Brain ischemia and reperfusion: molecular mechanisms of neuronal injury

Journal of the Neurological Sciences - Tập 179 - Trang 1-33 - 2000
Blaine C White1,2, Jonathon M Sullivan1, Donald J DeGracia1,2, Brian J O’Neil1, Robert W Neumar3, Lawrence I Grossman4, José A Rafols5, Gary S Krause1
1Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, USA
2Department of Physiology, Wayne State University School of Medicine, Detroit, MI USA
3Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA
4Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA
5Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA

Tài liệu tham khảo

Direct costs were calculated by Thomas A. Hodgson, chief economist and acting director, Division of Health and Utilization Analysis, OAEHP, NCHS, CDC. Estimates of indirect costs were made by Thomas J. Thom, statistician in the Division of Epidemiology and Clinical Applications, NHLBI. Krause, 1986, Ischemia, resuscitation, and reperfusion: mechanisms of tissue injury and prospects for protection, Am Heart J, 111, 768, 10.1016/0002-8703(86)90114-6 1986, Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest, New Engl J Med, 314, 397, 10.1056/NEJM198602133140701 1991, A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest, New Engl J Med, 324, 1225, 10.1056/NEJM199105023241801 1996, A randomized trial of trilazad mesylate in patients with acute stroke, Stroke, 27, 1453, 10.1161/01.STR.27.9.1453 Davis, 2000, Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist, Stroke, 31, 347, 10.1161/01.STR.31.2.347 Krause, 1988, Brain cell death following ischemia and reperfusion: a proposed biochemical sequence, Crit Care Med, 16, 714, 10.1097/00003246-198807000-00015 Hossman, 1976, Cerebral uptake of glucose and oxygen in the cat brain after prolonged ischemia, Stroke, 7, 301, 10.1161/01.STR.7.3.301 Siesjo, 1973, Cerebral energy reserves after prolonged hypoxia and ischemia, Arch Neurol, 29, 400, 10.1001/archneur.1973.00490300062008 Negovskii, 1962 Jenkins, 1981, The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia, Acta Neuropathol, 5, 205, 10.1007/BF00691320 Kumar, 1987, Ultrastructural and ionic changes in global ischemic dog brain, Acta Neuropathol (Berlin), 73, 393, 10.1007/BF00688266 Sato, 1990, Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells, Acta Neuropathol (Berlin), 80, 527, 10.1007/BF00294614 Ames, 1968, Cerebral ischemia II: the no-reflow phenomenon, Am J Pathol, 52, 437 Cerchiari, 1987, Protective effects of combined superoxide dismutase and deferoxamine on recovery of cerebral blood flow and function after cardiac arrest in dogs, Stroke, 18, 869, 10.1161/01.STR.18.5.869 Hall, 1988, Attenuation of post-ischemic cerebral hypoperfusion by the 21-aminosteroid U74006F, Stroke, 10, 340, 10.1161/01.STR.19.3.340 Braughler, 1987, Novel 21-amino steroids as potent inhibitors of iron-dependent lipid peroxidation, J Biol Chem, 262, 10438, 10.1016/S0021-9258(18)60979-2 Hossman, 1973, Reversibility of ischemic brain damage, Arch Neurol, 29, 375, 10.1001/archneur.1973.00490300037004 Meis, 1990, Cerebral blood flow, glucose utilization, regional glucose, and ATP content during the maturation period of delayed ischemic injury in gerbil brain, J Cereb Blood Flow Metab, 10, 638, 10.1038/jcbfm.1990.116 White, 1985, Prolonged cardiac arrest and resuscitation in dogs. Brain mitochondrial function with different artificial perfusion methods, Ann Emerg Med, 14, 383, 10.1016/S0196-0644(85)80278-X Cooper, 1977, The effect of ischemia and recirculation on protein synthesis in the rat brain, J Neurochem, 28, 929, 10.1111/j.1471-4159.1977.tb10652.x Dienel, 1980, Regional protein synthesis in rat brain following acute hemispheric ischemia, J Neurochem, 35, 1216, 10.1111/j.1471-4159.1980.tb07878.x Siesjö, 1992, Pathophysiology and treatment of focal cerebral ischemia. I. Pathophysiology, J Neurosurg, 77, 169, 10.3171/jns.1992.77.2.0169 Schoepp, 1993, Metabotropic glutamate receptors in brain function and pathology, TIPS, 14, 13 Siliprandi, 1992, Activation of glutamate metabotropic receptor protects retina against N-methyl-d-aspartate toxicity, Eur J Pharmacol, 219, 173, 10.1016/0014-2999(92)90598-X Lipartiti, 1993, In rats, the metaboprobic receptor-triggered hippocampal neuronal damage is strain-dependent, Life Sci, 52, PL85, 10.1016/0024-3205(93)90522-5 Erecinska, 1992, Relationships between ions and energy metabolism: cerebral calcium movements during ischaemia and subsequent recovery, Can J Physiol Pharmacol, 70, S190, 10.1139/y92-262 Chan, 1983, Reductions of gamma-aminobutyric acid and glutamate and (Na++K+)-ATPase activity in brain slices and synaptosomes by arachidonic acid, J Neurochem, 40, 309, 10.1111/j.1471-4159.1983.tb11284.x Braughler, 1985, Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids, J Neurochem, 44, 1282, 10.1111/j.1471-4159.1985.tb08755.x Ames, 1983, Earliest irreversible changes during ischemia, Am J Emerg Med, 2, 139, 10.1016/0735-6757(83)90081-5 Drejer, 1985, Schousboe A: cellular origin of ischemic-induced glutamate release from brain tissue in vivo and in vitro, J Neurochem, 45, 145, 10.1111/j.1471-4159.1985.tb05486.x Traynelis, 1990, Proton inhibition of N-methyl-d-aspartate receptors in cerebellar neurons, Nature, 345, 347, 10.1038/345347a0 Nellgård, 1992, Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in the rat brain following severe cerebral ischemia, J Cereb Blood Flow Metab, 12, 2, 10.1038/jcbfm.1992.2 Abe, 1987, Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex, J Neurochem, 48, 503, 10.1111/j.1471-4159.1987.tb04121.x Drenth, 1976, Structure of porcine pancreatic phospholipase A2, Nature, 264, 373, 10.1038/264373a0 Moskowitz, 1984, Regulation of endogenous calcium-dependent synaptic membrane phospholipase A2, Brain Res, 290, 273, 10.1016/0006-8993(84)90944-2 Rehncrona, 1982, Brain cortical fatty acids and phospholipids during and following complete and severe incomplete ischemia, J Neurochem, 38, 84, 10.1111/j.1471-4159.1982.tb10857.x Bazan, 1970, Effects of ischemia and electroconvulsive shock on free fatty acid pools in the brain, Biochim Biophys Acta, 218, 1, 10.1016/0005-2760(70)90086-X Yasuda, 1985, Biphasic liberation of arachidonic and stearic acids during cerebral ischemia, J Neurochem, 45, 168, 10.1111/j.1471-4159.1985.tb05489.x Yoshida, 1980, Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain, J Neurosurg, 53, 323, 10.3171/jns.1980.53.3.0323 Katsuki, 1995, Arachidonic acid as a neurotoxic and neurotrophic substance, Prog Neurobiol, 46, 607, 10.1016/0301-0082(95)00016-O Umemura, 1990, Regional difference in free fatty acids release and the action of phospholipase during ischemia in rat brain, No To Shinkei, 42, 979 Demopoulos, 1980, The free radical pathology and the microcirculation in the major central nervous system disorders, Acta Physiol Scand, 492, 91 Ushijima, 1986, Immunohistochemical localization of glutathione peroxidase in the brain of the rat, Resuscitation, 13, 97, 10.1016/0300-9572(86)90013-4 Krause, 1987, Natural course of iron delocalization and lipid peroxidation following a 15 minute cardiac arrest in dogs, Ann Emerg Med, 16, 1200, 10.1016/S0196-0644(87)80224-X Zaleska, 1985, Regional lipid peroxidation in rat brain in vitro: possible role of endogenous iron, Neurochem Res, 10, 397, 10.1007/BF00964608 Halliwell, 1984, Oxygen toxicity, oxygen radicals, transition metals, and disease, Biochem J, 19, 1, 10.1042/bj2190001 Freeman, 1982, Free radicals and tissue injury, Lab Invest, 47, 412 Aust, 1985, Role of metals in oxygen radical reactions, J Free Radic Biol Med, 1, 3, 10.1016/0748-5514(85)90025-X Harrison, 1968, Trace elements in the human brain: copper, iron, and magnesium, Clin Chim Acta, 21, 55, 10.1016/0009-8981(68)90010-7 Crichton, 1979, Interactions between iron metabolism and oxygen activation, vol. 65, 57 Thomas, 1985, Ferritin and superoxide dependent lipid peroxidation, J Biol Chem, 260, 3275, 10.1016/S0021-9258(19)83617-7 Beckman, 1991, The double-edged role of nitric oxide in brain function and superoxide-mediated injury, J Dev Physiol, 15, 53 Samdani, 1997, Nitric oxide synthase in models of focal ischemia, Stroke, 28, 1283, 10.1161/01.STR.28.6.1283 Tanaka, 1997, Immunohistochemical detection of nitrotyrosine in postischemic cerebral cortex in gerbil, Neurosci Lett, 235, 85, 10.1016/S0304-3940(97)00725-8 Kogure, 1982, Potentiation of lipid peroxides by ischemia in rat brain, Neurochem Res, 7, 437, 10.1007/BF00965496 Watson, 1984, Lipid peroxidation in vivo induced by reversible global ischemia in rat brain, J Neurochem, 42, 268, 10.1111/j.1471-4159.1984.tb09728.x Bromont, 1989, Increased lipid peroxidation in vulnerable brain regions after transient forebrain ischemia in rats, Stroke, 20, 918, 10.1161/01.STR.20.7.918 Sakamoto, 1991, Relationship between free radical production and lipid peroxidation during ischemia-reperfusion injury in rat brain, Brain Res, 554, 186, 10.1016/0006-8993(91)90187-Z Rosenthal, 1992, Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine, Free Radic Biol Med, 12, 29, 10.1016/0891-5849(92)90055-L Janero, 1990, Malondialdehyde and thiobarbituric acid reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury, Free Radic Biol Med, 9, 515, 10.1016/0891-5849(90)90131-2 Kruman, 1999, Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis, J Neurosci, 17, 5089, 10.1523/JNEUROSCI.17-13-05089.1997 Lukacova, 1998, Lipid peroxidation and phospholipid composition in rat brain regions after ischemia and in early reperfusion periods, Arch Ital Biol, 136, 167 White, 1988, Effect of deferoxamine or superoxide dismutase therapy on biochemical markers of neuronal injury at 8 hours of reperfusion following a 15 minute cardiac arrest in dogs, Am J Emerg Med, 6, 569, 10.1016/0735-6757(88)90093-9 White, 1993, Fluorescent histochemical localization of lipid peroxidation during brain reperfusion, Acta Neuropathol (Berlin), 86, 1, 10.1007/BF00454891 Hall, 1997, Immunocytochemical method for investigating in vivo neuronal oxygen radical-induced lipid peroxidation, J Neurosci Methods, 76, 115, 10.1016/S0165-0270(97)00089-7 Yoshino, 1997, Postischemic accumulation of lipid peroxidation products in the rat brain: immunohistochemical detection of 4-hydroxy-2-nonenal modified proteins, Brain Res, 767, 81, 10.1016/S0006-8993(97)00616-1 Farquhar, 1978, Traffic of products and membranes through the Golgi complex, 341 Voelker, 1990, Lipid transport pathways in mammalian cells, Experientia, 46, 569, 10.1007/BF01939695 Sun, 1994, Ischemia-induced changes in cerebral mitochondrial free fatty acids, phospholipids, and respiration in the rat, J Neurochem, 62, 1921, 10.1046/j.1471-4159.1994.62051921.x Barker, 1975, Mechanisms of lipid peroxidation in erythrocytes of vitamin E deficient rats and in phospholipid model systems, Arch Biochem Biophys, 166, 32, 10.1016/0003-9861(75)90361-6 Sevanian, 1983, The influence of phospholipase A2 and glutathione peroxidase on the elimination of membrane lipid peroxides, Arch Biochem Biophys, 223, 441, 10.1016/0003-9861(83)90608-2 Au, 1985, Stimulation of phospholipase A2 activity by oxygen-derived free radicals in isolated brain capillaries, J Cell Biochem, 27, 449, 10.1002/jcb.240270413 Chan, 1982, Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices, J Neurochem, 38, 525, 10.1111/j.1471-4159.1982.tb08659.x Das, 1986, Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion, Am J Physiol, 251, H71 Zaleska, 1989, Lipid hydroperoxides inhibit reacylation of phospholipids in neuronal membranes, J Neurochem, 52, 255, 10.1111/j.1471-4159.1989.tb10925.x O’Neil, 1999, Cell death, calcium mobilization, and immunostaining for phosphorylated eukaryotic initiation factor 2-alpha (eIF2α) in neuronally-differentiated NB-104 cells: arachidonate and radical-mediated injury mechanisms, Resuscitation, 41, 71, 10.1016/S0300-9572(99)00028-3 Sterz, 1989, No improved outcome after prolonged cardiac arrest and treatment with excitatory neurotransmitter receptor blocker MK-801 in dogs, Ann Emerg Med, 18, 456, 10.1016/S0196-0644(89)80708-5 Pellegrini-Giampietro, 1990, Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage, J Neurosci, 10, 1035, 10.1523/JNEUROSCI.10-03-01035.1990 Kumar, 1988, A quantitative morphological assessment of the effect of lidoflazine and deferoxamine therapy for global brain ischemia, Neurol Res, 10, 136, 10.1080/01616412.1988.11739830 Rosenthal, 1992, Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine, Free Radic Biol Med, 12, 29, 10.1016/0891-5849(92)90055-L Natale, 1988, Effect of the aminosteroid U74006F after cardiopulmonary arrest in dogs, Stroke, 19, 1371, 10.1161/01.STR.19.11.1371 Sterz, 1991, Effects of U74006F on multifocal cerebral blood flow and metabolism after cardiac arrest in dogs, Stroke, 22, 889, 10.1161/01.STR.22.7.889 Skjaerlund, 1991, The effect of EMHP on post-cardiac arrest survival of rats, Resuscitation, 22, 139, 10.1016/0300-9572(91)90004-I Pierucci, 1985, Duplication of E. coli during inhibition of net phospholipid synthesis, J Bacteriol, 162, 374, 10.1128/JB.162.1.374-382.1985 Joseleau-Petit, 1987, DNA replication initiation, doubling of rate of phospholipid synthesis, and cell division in E. coli, J Bacteriol, 169, 3701, 10.1128/jb.169.8.3701-3706.1987 Loewy, 1990, Regulatory interactions between phospholipid synthesis and DNA replication in Caulobacter crescentus, J Bacteriol, 172, 5523, 10.1128/jb.172.10.5523-5530.1990 Contreras, 1979, Caulobacter cresentus mutant defective in membrane phospholipid synthesis, J Bacteriol, 140, 612, 10.1128/JB.140.2.612-619.1979 Cooper, 1981, Inhibition of sterol and phospholipid synthesis in HL-60 promyelocytic leukemia cells by inducers of myeloid differentiation, Cancer Res, 41, 1847 Siperstein, 1984, Role of cholesterogenesis and isoprenoid synthesis in DNA replication and cell growth, J Lipid Res, 25, 1462, 10.1016/S0022-2275(20)34419-9 Benedetti, 1984, Loss of lipid peroxidation as a histochemical marker for preneoplastic hepatocellular foci of rats, Cancer Res, 44, 5712 Dianzani, 1989, Lipid peroxidation and cancer: a critical reconsideration, Tumori, 75, 351, 10.1177/030089168907500410 O’Neil, 1996, Ultrastructural consequences of radical damage before and after differentiation of neuroblastoma-104 cells, Acta Neuropathol (Berlin), 92, 75, 10.1007/s004010050492 Guroff, 1984, A neutral calcium-activated protease from the soluble fraction of rat brain, J Biol Chem, 239, 149, 10.1016/S0021-9258(18)51762-2 Goll, 1990, Historical background and current status of the Ca2+-dependent proteinase system, 3 Croall, 1991, Calcium-activated neutral protease (Calpain) system: structure, function, and regulation, Physiol Rev, 3, 813, 10.1152/physrev.1991.71.3.813 Goll, 1992, Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin, BioEssays, 14, 549, 10.1002/bies.950140810 Siman, 1985, Distribution of calpain I, an enzyme associated with degenerative activity in rat brain, Brain Res, 347, 399, 10.1016/0006-8993(85)90208-2 Hamakubo, 1986, Distribution of calpains I and II in rat brain, J Neurosci, 6, 3103, 10.1523/JNEUROSCI.06-11-03103.1986 Fukuda, 1990, Immunohistochemical distribution of calcium-activated neutral proteinases and endogenous CANP inhibitor in the rabbit hippocampus, J Comp Neurol, 302, 100, 10.1002/cne.903020108 Kamakura, 1992, Distribution of calcium-activated neutral protease inhibitor in the central nervous system of the rat, J Neurosci Res, 31, 543, 10.1002/jnr.490310318 Song, 1994, Calpain inhibitors block Ca(2+)-induced suppression of neurite outgrowth in isolated hippocampal pyramidal neurons, J Neurosci Res, 39, 474, 10.1002/jnr.490390414 Seubert, 1990, Plasticity and pathology: brain calpains as modifiers of synaptic structure, 251 Siman, 1989, Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage, J Neurosci, 9, 1579, 10.1523/JNEUROSCI.09-05-01579.1989 Schlaepfer, 1985, Mechanisms underlying the neuronal response to ischemic injury. Calcium-activated proteolysis of neurofilaments, Prog Brain Res, 63, 185, 10.1016/S0079-6123(08)61983-4 Seubert, 1989, Ischemia triggers NMDA receptor-linked cytoskeletal proteolysis in hippocampus, Brain Res, 492, 366, 10.1016/0006-8993(89)90921-9 Lee, 1991, Inhibition of proteolysis protects hippocampal neurons from ischemia, Proc Natl Acad Sci USA, 88, 7233, 10.1073/pnas.88.16.7233 Rami, 1993, Protective effects of calpain inhibitors against neuronal damage caused by cytotoxic hypoxia in vitro and ischemia in vivo, Brain Res, 609, 67, 10.1016/0006-8993(93)90856-I Roberts-Lewis, 1993, Spectrin proteolysis in the hippocampus: a biochemical marker for neuronal injury and neuroprotection, Ann New York Acad Sci, 679, 78, 10.1111/j.1749-6632.1993.tb18290.x Saido, 1993, Spatial resolution of fodrin proteolysis in postischemic brain, J Biol Chem, 268, 25239, 10.1016/S0021-9258(19)74593-1 Saito, 1993, Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration, Proc Natl Acad Sci USA, 90, 2628, 10.1073/pnas.90.7.2628 Squier, 1994, Calpain activation in apoptosis, J Cell Physiol, 159, 229, 10.1002/jcp.1041590206 Suzuki, 1990, The structure of the calpains and the calpain gene, 25 Maki, 1990, Structure–function relationships of calpastatins, 37 Suzuki, 1992, Modulation of cellular signals by calpain, Ann New York Acad Sci, 674, 218, 10.1111/j.1749-6632.1992.tb27490.x Croall, 1990, Regulation of calcium-dependent protease activity in vitro: clues for determining their physiological functions, 103 Hayashi, 1991, Activation of intracellular calcium-activated neutral proteinase in erythrocytes and its inhibition by exogenously added inhibitors, Biochim Biophys Acta, 1094, 249, 10.1016/0167-4889(91)90083-A Cong, 1989, The role of autolysis in activity of the Ca2+-dependent proteinases (μ-calpain and m-calpain), J Biol Chem, 264, 10096, 10.1016/S0021-9258(18)81771-9 Kuboki, 1987, Procalpain is activated on the plasma membrane and the calpain acts on the membrane, Biochim Biophys Acta, 929, 164, 10.1016/0167-4889(87)90172-8 Saido, 1992, Positive regulation of μ-calpain action by polyphosphoinositides, J Biol Chem, 267, 24585, 10.1016/S0021-9258(18)35804-6 Neumar, 1996, Brain μ-calpain autolysis during global cerebral ischemia, J Neurochem, 66, 421, 10.1046/j.1471-4159.1996.66010421.x Ruiz-Vela, 1999, Implication of calpain in caspase activation during B cell clonal deletion, EMBO J, 18, 4988, 10.1093/emboj/18.18.4988 Kleihues, 1971, Protein synthesis in the cat brain after prolonged cerebral ischemia, Brain Res, 35, 409, 10.1016/0006-8993(71)90484-7 Cooper, 1977, The effect of ischemia and recirculation on protein synthesis in the rat brain, J Neurochem, 28, 929, 10.1111/j.1471-4159.1977.tb10652.x Nowak, 1985, Changes in brain energy metabolism and protein synthesis following transient bilateral ischemia in the gerbil, J Neurochem, 44, 487, 10.1111/j.1471-4159.1985.tb05440.x Bodsch, 1985, Cerebral protein synthesis and ischemia, Prog Brain Res, 63, 197, 10.1016/S0079-6123(08)61984-6 Bodsch, 1986, Recovery of monkey brain after prolonged ischemia II. Protein synthesis and morphologic alterations, J Cereb Blood Flow Metab, 6, 22, 10.1038/jcbfm.1986.4 Thilmann, 1986, Persistent inhibition of protein synthesis precedes delayed neuronal death in post-ischemic gerbil hippocampus, Acta Neuropathol (Berlin), 71, 88, 10.1007/BF00687967 Yoshidomi, 1989, Effects of a new calcium channel blocker, KB-2796, on protein synthesis of the CA1 pyramidal cell and delayed neuronal death following transient forebrain ischemia, J Neurochem, 53, 1589, 10.1111/j.1471-4159.1989.tb08556.x Araki, 1990, Regional impairment of protein synthesis following brief cerebral ischemia in the gerbil, Acta Neuropathol, 79, 501, 10.1007/BF00296109 Widmann, 1991, [14C]-Leucine incorporation into brain proteins in gerbils after transient ischemia: relationship to selective vulnerability of hippocampus, J Neurochem, 56, 789, 10.1111/j.1471-4159.1991.tb01993.x Pulsinelli, 1982, Temporal profile of neuronal damage in a model of transient forebrain ischemia, Ann Neurol, 11, 491, 10.1002/ana.410110509 Furuta, 1993, Recovery of protein synthesis in tolerance-induced hippocampal CA1 neurons after transient forebrain ischemia, Acta Neuropathol (Berlin), 86, 329, 10.1007/BF00369444 O’Neil, 1991, Thymine glycols and pyrimidine dimers in brain DNA during post-ischemic reperfusion, Resuscitation, 21, 41, 10.1016/0300-9572(91)90077-C White, 1991, Brain DNA survives cardiac arrest and reperfusion, Free Radic Biol Med, 10, 125, 10.1016/0891-5849(91)90006-O White, 1992, Brain mitochondrial DNA is not damaged by prolonged cardiac arrest or reperfusion, J Neurochem, 58, 1716, 10.1111/j.1471-4159.1992.tb10045.x Lindvall, 1992, Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 in the adult rat brain following cerebral ischemia and hypoglycemic coma, Proc Natl Acad Sci USA, 89, 648, 10.1073/pnas.89.2.648 Xie, 1989, Determination of RNA content in postischemic gerbil brain by in situ hybridization, Metab Brain Dis, 4, 239, 10.1007/BF00999770 Nowak, 1990, 70 kDa heat shock protein and c-fos gene expression after transient ischemia, Stroke, 21, 107 Onodera, 1989, Proto-oncogene c-fos is transiently induced in the rat cerebral cortex after forebrain ischemia, Neurosci Lett, 98, 101, 10.1016/0304-3940(89)90381-9 Kindy, 1991, Ischemic induction of protooncogene expression in gerbil brain, J Mol Neurosci, 2, 217 Matsumoto, 1990, RNA synthesis and processing in the gerbil brain after transient hindbrain ischaemia, Neurol Res, 12, 45, 10.1080/01616412.1990.11739912 Tiffany, 1995, Nuclear-envelope nucleoside triphosphatase kinetics and mRNA transport following brain ischemia and reperfusion, Ann Emerg Med, 25, 809, 10.1016/S0196-0644(95)70213-X Krause, 1993, Assessment of free radical-induced damage in brain proteins after ischemia and reperfusion, Resuscitation, 23, 59, 10.1016/0300-9572(92)90162-6 Roberts, 1976, Role of ribonuclease action in phenylalanine-induced disaggregation of rat cerebral polyribosomes, J Neurochem, 26, 387, 10.1111/j.1471-4159.1976.tb04492.x DeGracia, 1993, Studies of the protein synthesis system in the brain cortex during global ischemia and reperfusion, Resuscitation, 21, 161, 10.1016/0300-9572(93)90092-5 Nowak, 1984, An in vitro amino acid incorporation method for assessing the status of in vivo protein synthesis, Anal Biochem, 136, 285, 10.1016/0003-2697(84)90218-5 Raley-Susman, 1990, In vitro ischemia and protein synthesis in the rat hippocampal slice: the role of calcium and NMDA receptor activation, Brain Res, 515, 27, 10.1016/0006-8993(90)90572-S Gaitero, 1988, Purification of a novel heat-stable translational inhibitor from rabbit reticulocyte lysates, FEBS Lett, 236, 479, 10.1016/0014-5793(88)80081-4 DeGracia, 1996, Global brain ischemia and reperfusion: modifications in eukaryotic initiation factors are associated with inhibition of translation initiation, J Neurochem, 67, 2005, 10.1046/j.1471-4159.1996.67052005.x Merrick, 1992, Mechanism and regulation of eukaryotic protein synthesis, Microbiol Rev, 56, 291, 10.1128/MR.56.2.291-315.1992 Rowlands, 1988, The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2, J Biol Chem, 263, 5526, 10.1016/S0021-9258(18)60596-4 Alcàzar, 1995, Purification and characterization of guinine nucleotide-exchange factor, eIF-2B, and p37 calmodulin-binding protein from calf brain, J Neurochem, 65, 754, 10.1046/j.1471-4159.1995.65020754.x Martin, 1993, Translation initiation factor eIF-2 subcellular levels and phosphorylation in the developing rat brain, Neurosci Lett, 156, 109, 10.1016/0304-3940(93)90451-P Ray, 1983, Role of mRNA competition in regulating translation. Further characterization of mRNA discriminatory initiation factors, Proc Natl Acad Sci USA, 80, 663, 10.1073/pnas.80.3.663 Duncan, 1987, Regulated phosphorylation and low abundance of HeLa cell initiation factor eIF-4F suggest a role in translational control. Heat shock effects on eIF-4F, J Biol Chem, 262, 380, 10.1016/S0021-9258(19)75938-9 Morley, 1990, Differential stimulation of initiation factors eIF-4F, eIF-4B, eIF-3 and ribosomal protein S6 by insulin and phorbal esters, J Biol Chem, 265, 10611, 10.1016/S0021-9258(18)86990-3 Schroder, 1990, Differential effect of insulin and epidermal growth factor on the mRNA translocation system and transport of specific poly-A(+) mRNA and poly-A(−) mRNA in isolated nuclei, Biochemistry, 29, 2368, 10.1021/bi00461a022 Bu, 1991, Platelet-derived growth factor stimulates phosphorylation of the 25 kDa mRNA cap binding protein (eIF-4E) in human lung fibroblasts, FEBS Lett, 283, 219, 10.1016/0014-5793(91)80592-Q Frederickson, 1992, Phosphorylation of translation initiation factor eIF-4E is induced in a ras-dependent manner during nerve growth factor-mediated PC12 cell differentiation, Mol Cell Biol, 12, 1239, 10.1128/MCB.12.3.1239 Donaldson, 1991, Epidermal growth factor or okadaic acid stimulates phosphorylation of eukaryotic initiation factor 4F, J Biol Chem, 266, 3162, 10.1016/S0021-9258(18)49968-1 Bu, 1993, Novel phosphorylation sites of eukaryotic initiation factor-4F and of the p25 and p220 subunits, J Biol Chem, 268, 4975, 10.1016/S0021-9258(18)53491-8 Morley, 1991, Phosphorylation of eIF-4F by protein kinase C or multipotential S6 kinase stimulates protein synthesis at initiation, J Biol Chem, 266, 4669, 10.1016/S0021-9258(19)67700-8 Clemens, 1998, Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines, Oncogene, 17, 2921, 10.1038/sj.onc.1202227 Neumar, 1998, Calpain I mediates eukaryotic initiation factor 4G degradation during global brain ischemia, J Cereb Blood Flow Metab, 18, 876, 10.1097/00004647-199808000-00007 DeGracia, 1997, Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2α, J Cereb Blood Flow Metab, 17, 1291, 10.1097/00004647-199712000-00004 Goldstein, 1999, Ultrastructural localization of phosphorylated eIF2α [eIF2α(P)] in rat dorsal hippocampus during reperfusion, Acta Neuropathol (Berlin), 98, 493, 10.1007/s004010051115 McKeown, 1999, Nuclear localization and DNA binding properties of phosphorylated eIF2α in vulnerable hippocampal neurons during reperfusion, J Cereb Blood Flow Metab, 19, S510 Sullivan, 1999, Insulin induces dephosphorylation of eIF2α and restores protein synthesis in vulnerable hippocampal neurons following transient brain ischemia, J Cereb Blood Flow Metab, 19, 1010, 10.1097/00004647-199909000-00009 Scorsone, 1987, Phosphorylation of eukaryotic initiation factor 2 during physiological stresses which affect protein synthesis, J Biol Chem, 262, 14538, 10.1016/S0021-9258(18)47829-5 Duncan, 1984, Heat shock-induced translational alterations in HeLa cells, J Biol Chem, 259, 11882, 10.1016/S0021-9258(20)71294-9 Zapata, 1991, Inactivation of mRNA cap-binding protein complex in Drosophila melanogaster embryos under heat shock, J Biol Chem, 266, 16007, 10.1016/S0021-9258(18)98508-X Lamphear, 1990, Cap binding protein complex that restores protein synthesis in heat-shocked Erlich cell lysates contains highly phosphorylated eIF-4E, J Biol Chem, 265, 5333, 10.1016/S0021-9258(19)39358-5 Lamphear, 1991, Heat shock impairs the interaction of cap-binding protein complex with 5′ mRNA cap, J Biol Chem, 266, 2789, 10.1016/S0021-9258(18)49916-4 Joshi-Barve, 1992, Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4γ, J Biol Chem, 267, 21038, 10.1016/S0021-9258(19)36794-8 Nowak, 1990, Heat shock RNA levels in brain and other tissues after hyperthermia and transient ischemia, J Neurochem, 54, 451, 10.1111/j.1471-4159.1990.tb01893.x Nowak, 1990, Protein synthesis and the heat shock/stress response after ischemia, Cerebrovasc Brain Metab Rev, 2, 345 Dever, 1995, Modulation of tRNAiMet, eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the levels of eIF-2-GTP-Met-tRNAiMet ternary complexes, Mol Cell Biol, 15, 6351, 10.1128/MCB.15.11.6351 Gan, 1996, Internal initiation of translation directed by the 5′-untranslated region of the mRNA for eIF-4G, a factor involved in the picornovirus-induced switch from cap-dependent to internal initiation, J Biol Chem, 27, 623, 10.1074/jbc.271.2.623 Ohlmann, 1996, The C-terminal domain of eukaryotic protein synthesis initiation factor eIF-4G is sufficient to support cap-independent translation in the absence of eIF-4E, EMBO J, 15, 1371, 10.1002/j.1460-2075.1996.tb00479.x Coldwell, 2000, Initiation of APAF-1 translation by internal ribosome entry, Oncogene, 19, 899, 10.1038/sj.onc.1203407 Stein, 1998, Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia, Mol Cell Biol, 18, 3112, 10.1128/MCB.18.6.3112 Vagner, 1996, Translation of CUG- but not AUG-initiated forms of human fibroblast growth factor-2 is activated in transformed and stressed cells, J Cell Biol, 135, 1391, 10.1083/jcb.135.5.1391 Martin, 1988, Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation, J Cell Biol, 106, 829, 10.1083/jcb.106.3.829 Shigeno, 1990, Reduction of delayed neuronal death by inhibition of protein synthesis, Neurosci Lett, 120, 117, 10.1016/0304-3940(90)90182-9 Wek, 1994, eIF-2 kinases: regulators of general and gene-specific translation initiation, TIBS, 19, 491 Samuel, 1993, The eIF-2α protein kinases, regulators of translation in eukaryotes from yeasts to humans, J Biol Chem, 268, 7603, 10.1016/S0021-9258(18)52994-X Harding, 1999, Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase, Nature, 397, 271, 10.1038/16729 Santoyo, 1997, Cloning and characterization of a cDNA encoding a protein synthesis initiation factor-2α (eIF-2α) kinase from Drosophila melanogaster, J Biol Chem, 272, 12544, 10.1074/jbc.272.19.12544 Sood, 2000, A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2α, Genetics, 154, 787, 10.1093/genetics/154.2.787 Donze, 1999, HSP90 binds and regulates the ligand-inducible alpha subunit of eukaryotic translation initiation factor kinase GCN2, Mol Cell Biol, 19, 8422, 10.1128/MCB.19.12.8422 Xiao, 1999, Geldanamycin provides posttreatment protection against glutamate-induced oxidative toxicity in a mouse hippocampal cell line, J Neurochem, 72, 95, 10.1046/j.1471-4159.1999.0720095.x Waskiewicz, 1988, Hypoxia and ischemia modifies histamine metabolism and transport in brain synaptosomes, Resuscitation, 16, 287, 10.1016/0300-9572(88)90115-3 Karkeela, 1993, Critical evaluation of postmortem changes in human cisternal fluid. Enzymes, electrolytes, acid–base balance, glucose and glycolysis, free amino acids, and ammonia. Correlation to total brain ischemia, J Forensic Sci, 38, 603, 10.1520/JFS13445J Kawamoto, 1997, Protective effect of l-histidine (singlet oxygen scavenger) on transient forebrain ischemia in the rat, No To Shinkei, 49, 612 Rolfes, 1993, Translation of the yeast transcriptional activator GCN4 is stimulated by purine limitation: implications for activation of the protein kinase GCN2, Mol Cell Biol, 13, 5099, 10.1128/MCB.13.8.5099 Newman, 1998, Restoring adenine nucleotides in a brain slice model of cerebral reperfusion, J Cereb Blood Flow Metab, 18, 675, 10.1097/00004647-199806000-00010 Hurst, 1987, Inhibition of rabbit reticulocyte lysate protein synthesis by heavy metal ions involves the phosphorylation of the α-subunit of the eukaryotic initiation factor 2, J Biol Chem, 262, 15939, 10.1016/S0021-9258(18)47679-X De Herreros, 1985, Mechanism of activation of the heme-stabilized translational inhibitor of reticulocyte lysates by calcium ions and phospholipid, Proc Natl Acad Sci USA, 82, 3119, 10.1073/pnas.82.10.3119 Pal, 1991, Tissue distribution of heme-regulated eIF-2α kinase determined by monoclonal antibodies, Biochemistry, 30, 2555, 10.1021/bi00223a037 Haines, 1993, Expression of p68 protein kinase as recognized by the monoclonal antibody TJ4C4 during human fetal development, Tumor Biol, 14, 95, 10.1159/000217828 Thomas, 1995, Mechanism of interferon action: characterization of the intermolecular autophosphorylation of PKR, the interferon-inducible, RNA-dependent protein kinase, J Virol, 69, 5195, 10.1128/JVI.69.8.5195-5198.1995 Proud, 1995, PKR: a new name and new roles, TIBS, 20, 241 Petryshyn, 1994, Activation of the dsRNA-dependent kinase, Prog Mol Subcell Biol, 14, 1, 10.1007/978-3-642-78549-8_1 Jagus, 1994, Proteins that interact with PKR, Biochimie, 76, 779, 10.1016/0300-9084(94)90082-5 Der, 1997, A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis, Proc Natl Acad Sci USA, 94, 3279, 10.1073/pnas.94.7.3279 Takizawa, 1995, Activation of the apoptotic FAS antigen-encoding gene upon influenza virus infection involving spontaneously produced β-interferon, Virology, 209, 288, 10.1006/viro.1995.1260 Schwemmle, 1992, Localization of Epstein–Barr virus-encoded RNAs EBER-1 and EBER-2 in interphase and mitotic Burkitt lymphoma cells, Proc Natl Acad Sci USA, 89, 10292, 10.1073/pnas.89.21.10292 Jeffrey, 1995, Nuclear localization of the interferon-inducible protein kinase PKR in human cells and transfected mouse cells, Exp Cell Res, 218, 17, 10.1006/excr.1995.1126 Bandyopadhyhay, 1992, Role of protein phosphorylation in activation of interferon-stimulated gene factors, J Biol Chem, 267, 6389, 10.1016/S0021-9258(18)42707-X DeGracia, 1998, Eukaryotic initiation factor 2α (eIF2α) kinase and phosphatase activity during post-ischemic brain reperfusion, Exp Neurol, 155, 221, 10.1006/exnr.1998.6986 Kaufman, 1999, Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls, Genes Dev, 13, 1211, 10.1101/gad.13.10.1211 Brostrom, 1983, Identification of a Ca2+ requirement for protein synthesis in eukaryotic cells, J Biol Chem, 258, 14390, 10.1016/S0021-9258(17)43874-9 Brostrom, 1985, Regulation of protein synthesis in isolated hepatocytes by calcium-mobilizing hormones, Mol Pharmocol, 29, 104 Chin, 1987, Calcium-dependent regulation of protein synthesis at translational initiation in eukaryotic cells, J Biol Chem, 262, 16509, 10.1016/S0021-9258(18)49285-X Brostrom, 1989, Inhibition of translation initiation in eukaryotic cells by calcium ionophore, J Biol Chem, 264, 1644, 10.1016/S0021-9258(18)94235-3 Kumar, 1989, Mechanism of inhibition of polypeptide chain initiation in calcium-depleted Erlick ascites tumor cells, J Cell Biol, 108, 2107, 10.1083/jcb.108.6.2107 Kimball, 1992, Regulation of protein synthesis by modulation of intracellular calcium in rat liver, Endocrinol Metab, 26, E958 Prostko, 1992, Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbation of early protein processing that induce GRP78, J Biol Chem, 267, 16751, 10.1016/S0021-9258(18)41842-X Prostko, 1993, Reversible phosphorylation of eukaryotic initiation factor 2 alpha in response to endoplasmic reticular signaling, Mol Cell Biochem, 127/128, 255, 10.1007/BF01076776 Kimball, 1991, Mechanism of inhibition of peptide chain initiation by amino acid deprivation in perfused rat liver, J Biol Chem, 266, 1969, 10.1016/S0021-9258(18)52387-5 Cohen, 1989, The structure and regulation of protein phosphatases, Annu Rev Biochem, 58, 453, 10.1146/annurev.bi.58.070189.002321 Ingebritsen, 1983, The protein phosphatases involved in cellular regulation. 1. Classification and substrate specificities, Eur J Biochem, 132, 255, 10.1111/j.1432-1033.1983.tb07357.x Redpath, 1990, Activity of protein phosphatases against initiation factor-2 and elongation factor-2, Biochem J, 272, 175, 10.1042/bj2720175 Ernst, 1982, Effects of skeletal muscle protein phosphatase inhibitor-2 on protein synthesis and protein phosphorylation in rabbit reticulocyte lysates, Proc Natl Acad Sci USA, 79, 7092, 10.1073/pnas.79.23.7092 Foulkes, 1983, Separation and identification of type 1 and type 2 protein phosphatases from rabbit reticulocyte lysates, J Biol Chem, 258, 1439, 10.1016/S0021-9258(18)33005-9 Takizawa, 1994, Tissue distribution of isoforms of type-1 protein phosphatase (PP1) in mouse tissue and its diabetic alteration, J Biochem, 116, 411, 10.1093/oxfordjournals.jbchem.a124540 Ouimet, 1995, The alpha and gamma 1 isoforms of protein phosphatase 1 are highly and specifically concentrated in dendritic spines, Proc Natl Acad Sci USA, 92, 3396, 10.1073/pnas.92.8.3396 daCruz e Silva, 1995, Differential expression of protein phosphatase 1 isoforms in mammalian brain, J Neurosci, 15, 3375, 10.1523/JNEUROSCI.15-05-03375.1995 Lee, 1999, Phosphorylase phosphatase: new horizons for an old enzyme, Front Biosci, 4, 270, 10.2741/Lee He, 1997, Proc Natl Acad Sci USA, 94, 843, 10.1073/pnas.94.3.843 Szyszka, 1989, A type 1 phosphoprotein phosphatase active with phosphorylated Mr=68,000 initiation factor 2 kinase, J Biol Chem, 264, 3827, 10.1016/S0021-9258(19)84925-6 Hubbard, 1993, On target with a new mechanism for the regulation of protein phosphorylation, Trends Biochem Sci, 18, 172, 10.1016/0968-0004(93)90109-Z Srinivasan, 1994, Regulation of protein phosphatase 1 and 2A activities by insulin during myogenesis in rat skeletal muscle cells in culture, J Biol Chem, 269, 12514, 10.1016/S0021-9258(18)99905-9 Chen, 1992, Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation, Science, 257, 1261, 10.1126/science.1325671 Katayose, 2000, Protein phosphatase 2A inhibitors, I1PP2A and I2PP2A, associate with and modify the substrate specificity of protein phosphatase 1, J Biol Chem, 275, 9209, 10.1074/jbc.275.13.9209 Oliver, 1998, Physiologic importance of protein phosphatase inhibitors, Front Biosci, 3, 961, 10.2741/A336 Cohen, 1988, Protein phosphatase inhibitor-1 and inhibitor-2 from rabbit skeletal muscle, Methods Enzymol, 59, 427, 10.1016/0076-6879(88)59042-0 Foulkes, 1980, The hormonal control of glycogen metabolism: dephosphorylation of protein phosphatase inhibitor-1 in vivo in response to insulin, FEBS Lett, 112, 21, 10.1016/0014-5793(80)80117-7 Chan, 1988, Stimulation of protein phosphatase activity by insulin and growth factors in 3T3 cells, Proc Natl Acad Sci USA, 85, 6257, 10.1073/pnas.85.17.6257 Hemmings, 1992, Distribution of protein phosphatase inhibitor-1 in brain and peripheral tissues of various species: comparison with DARPP-32, J Neurochem, 59, 1053, 10.1111/j.1471-4159.1992.tb08347.x Lowenstein, 1995, Immunolocalization of protein phosphatase inhibitor-1 in the cerebral cortex of the rat, cat, and ferret, Brain Res, 676, 80, 10.1016/0006-8993(95)00091-4 Voll, 1991, Insulin attenuates ischemic brain damage independent of its hypoglycemic effect, J Cereb Blood Flow Metab, 11, 1006, 10.1038/jcbfm.1991.168 Datta, 1988, Roles of a 67-kDa polypeptide in reversal of protein synthesis inhibition in heme-deficient reticulocyte lysate, Proc Natl Acad Sci USA, 85, 3324, 10.1073/pnas.85.10.3324 Chakraborty, 1994, Regulation of eIF-2 α-subunit phosphorylation in reticulocyte lysate, Biochemistry, 33, 6700, 10.1021/bi00187a041 Rehemtulla, 1996, A eukaryotic translation initiation factor 2-associated 67 kDa glycoprotein partially reverses protein synthesis inhibition by activated double-stranded RNA-dependent protein kinase in intact cells, Biochemistry, 35, 8275, 10.1021/bi953028+ Saha, 1997, Viral infection II: hemin induces overexpression of p67 as it partially prevents appearance of an active p67-deglycosylase in baculovirus-infected insect cells, Arch Biochem Biophys, 342, 373, 10.1006/abbi.1997.0139 Bose, 1997, Viral infection I: regulation of protein synthesis during vaccinia viral infection of animal cells, Arch Biochem Biophys, 342, 362, 10.1006/abbi.1997.0138 Owen, 2000, Characterization of the eIF2-associated protein p67 during brain ischemia and reperfusion, vol. IV Gerstenfeld, 1983, Cell-free translation of calf type III collagen: effect of magnesium on ribosome movement during elongation, J Biol Chem, 258, 12058, 10.1016/S0021-9258(17)44339-0 Peterrson, 1980, Ribosomal protein L7/L12 is required for optimal translation, Proc Natl Acad Sci USA, 77, 4007, 10.1073/pnas.77.7.4007 VanDuffel, 1975, Isolation and characterizations of active ribosomal subunits from human placenta, J Biochem, 57, 481 Hata, 2000, Dynamics of regional brain metabolism and gene expression after middle cerebral occlusion in mice, J Cereb Blood Flow Metab, 20, 306, 10.1097/00004647-200002000-00012 Bredesen, 1996, Keeping neurons alive: the molecular control of apoptosis, Neuroscientist, 2, 211, 10.1177/107385849600200409 Hale, 1995, Apoptosis: molecular regulation of cell death, Eur J Biochem, 236, 1, 10.1111/j.1432-1033.1996.00001.x Arends, 1990, Apoptosis. The role of the endonuclease, Am J Pathol, 136, 593 Jacobson, 1994, Programmed cell death and Bcl-2 protection in the absence of a nucleus, EMBO J, 13, 1899, 10.1002/j.1460-2075.1994.tb06459.x Ellis, 1991, Genes required for the engulfment of cell corpses during programmed cell death in C. elegans, Genetics, 129, 79, 10.1093/genetics/129.1.79 Nagata, 1995, The Fas death factor, Science, 267, 1449, 10.1126/science.7533326 Hu, 1999, Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-κB and JNK activation and apoptosis through distinct pathways, J Biol Chem, 274, 30603, 10.1074/jbc.274.43.30603 Ahmad, 1997, CRADD, a novel human apoptotic adaptor molecule for caspase-2 and FasL/tumor necrosis factor receptor-interacting protein RIP, Cancer Res, 57, 615 Muzio, 1997, FLICE-induced apoptosis in a cell-free system. Cleavage of caspase zymogens, J Biol Chem, 272, 2952, 10.1074/jbc.272.5.2952 Zhou, 1997, Target protease specificity of the viral serpin CrmA. Analysis of five caspases, J Biol Chem, 272, 7797, 10.1074/jbc.272.12.7797 Bertin, 1997, Death effector domain-containing herpesvirus and poxvirus proteins inhibit both FAS- and TNFR1-induced apoptosis, Proc Natl Acad Sci USA, 94, 1172, 10.1073/pnas.94.4.1172 Kajstura, 1996, Apoptotic and necrotic myocyte cell deaths are independent contributing variables in infarct size in rats, Lab Invest, 74, 86 Brömme, 1996, Apoptosis in the heart: when and why?, Mol Cell Biochem, 163/164, 261, 10.1007/BF00408667 Matsuyama, 1994, Fas antigen mRNA induction in postischemic murine brain, Brain Res, 657, 342, 10.1016/0006-8993(94)90989-X Martin-Villalba, 1999, CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons, J Neurosci, 19, 3809, 10.1523/JNEUROSCI.19-10-03809.1999 Herr, 1999, FK506 prevents stroke-induced generation of ceramide and apoptosis signaling, Brain Res, 826, 210, 10.1016/S0006-8993(99)01288-3 Roth, 1999, Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity, Biochem Biophys Res Commun, 265, 479, 10.1006/bbrc.1999.1693 Zhang, 1997, Tumor necrosis factor receptor expression following focal embolic cerebral ischemia in mice, J Cereb Blood Flow Metab, 17, S531 Bruce, 1996, Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors, Nat Med, 2, 788, 10.1038/nm0796-788 Reuther, 1999, Apoptosis promotes a caspase-induced amino-terminal truncation of IκBα that functions as a stable inhibitor of NF-κB, J Biol Chem, 274, 20664, 10.1074/jbc.274.29.20664 Natoli, 1998, Nuclear factor κB-independent cytoprotective pathways originating at tumor necrosis factor receptor-associated factor 2, J Biol Chem, 273, 31262, 10.1074/jbc.273.47.31262 Chu, 1997, Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-κB control, Proc Natl Acad Sci USA, 94, 10057, 10.1073/pnas.94.19.10057 Wang, 1998, NF-κB anti-apoptosis: induction of TRAF1 And TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation, Science, 281, 1680, 10.1126/science.281.5383.1680 Sarma, 1995, Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis, J Biol Chem, 270, 12343, 10.1074/jbc.270.21.12343 DeValck, 1999, The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases, Oncogene, 18, 4182, 10.1038/sj.onc.1202787 Darville, 2000, NF-κB is required for cytokine-induced manganese superoxide dismutase expression in insulin-producing cells, Endocrinology, 141, 153, 10.1210/en.141.1.153 Xu, 1999, Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus, J Neurosci, 19, 5026, 10.1523/JNEUROSCI.19-12-05026.1999 Li, 2000, Adenosine prevents activation of transcription factor NF-κB and enhances activator protein-1 binding activity in ischemic rat heart, Surgery, 127, 161, 10.1067/msy.2000.101582 Clemens, 1997, Global cerebral ischemia activates nuclear factor-kappaB prior to evidence of DNA fragmentation, Brain Res Mol Brain Res, 48, 187, 10.1016/S0169-328X(97)00092-2 Clemens, 1998, Drug-induced neuroprotection from global ischemia is associated with prevention of persistent but not transient activation of nuclear factor-kappaB, Stroke, 29, 677, 10.1161/01.STR.29.3.677 Botchkina, 1999, Loss of NF-κB activity during cerebral ischemia and TNF cytotoxicity, Mol Med, 5, 372, 10.1007/BF03402126 Zaifang, 1999, Lack of the p50 subunit of nuclear factor-κB increases the vulnerability of hippocampal neurons to excitotoxic injury, J Neurosci, 19, 8856, 10.1523/JNEUROSCI.19-20-08856.1999 Cain, 2000, Apaf-1 oligomerizes into biologically active ∼700-kDa and inactive ∼1.4 MDa apoptosome complexes, J Biol Chem, 275, 6067, 10.1074/jbc.275.9.6067 Irmler, 1997, Direct physical interaction between the C. elegans ‘death proteins’ CED-3 and CED-4, FEBS Lett, 406, 189, 10.1016/S0014-5793(97)00271-8 James, 1997, CED-4 induces chromatin condensation in S. pombe and is inhibited by direct physical interaction with CED-9, Curr Biol, 7, 246, 10.1016/S0960-9822(06)00120-5 Spector, 1997, Interaction between the C. elegans cell-death regulators CED-9 and CED-4, Nature, 385, 653, 10.1038/385653a0 Zou, 1997, Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome-c-dependent activation of caspase 3, Cell, 90, 405, 10.1016/S0092-8674(00)80501-2 Krajewski, 1999, Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia, Proc Natl Acad Sci USA, 96, 5752, 10.1073/pnas.96.10.5752 Fujimura, 1998, Cytosolic redistribution of cytochrome-c after transient focal cerebral ischemia in rats, J Cereb Blood Flow Metab, 18, 1239, 10.1097/00004647-199811000-00010 Nakatsuka, 1999, Release of cytochrome-c from mitochondria to cytosol in gerbil hippocampal CA1 neurons after transient forebrain ischemia, Brain Res, 849, 216, 10.1016/S0006-8993(99)01971-X Andreyev, 1998, Cytochrome-c release from brain mitochondria is independent of the mitochondrial permeability transition, FEBS Lett, 439, 373, 10.1016/S0014-5793(98)01394-5 Blomgren, 1999, Caspase–calpain interaction and calpastatin as a stress protein in neonatal rat hypoxia-ischemia, J Cereb Blood Flow Metab, 19, S49 Datta, 1999, Cellular survival: a play in three Akts, Genes Dev, 13, 2905, 10.1101/gad.13.22.2905 Gillardon, 1997, Activation of CPP-32, an ICE-related protease, in hippocampal neurons following ischemia and epilepsy, J Cereb Blood Flow Metab, 17, S445 Martins, 1997, Activation of multiple interleukin-1β converting enzyme homologues in cytosol and nuclei of HL-60 cells during etoposide-induced apoptosis, J Biol Chem, 272, 7421, 10.1074/jbc.272.11.7421 Margolin, 1997, Substrate and inhibitor specificity of interleukin-1 beta-converting enzyme and related caspases, J Biol Chem, 272, 7223, 10.1074/jbc.272.11.7223 Van de Craen, 1997, Characterization of seven murine caspase family members, FEBS Lett, 403, 61, 10.1016/S0014-5793(97)00026-4 Le Romancer, 1996, Cleavage and inactivation of DNA-dependent protein kinase catalytic subunit during apoptosis in Xenopus egg extracts, J Cell Sci, 109, 3121, 10.1242/jcs.109.13.3121 Rosenthal, 1997, Detection of DNA breaks in apoptotic cells utilizing the DNA binding domain of poly(ADP-ribose) polymerase with fluorescence microscopy, Nucleic Acids Res, 15, 1437, 10.1093/nar/25.7.1437 Whitacre, 1995, Involvement of NAD-poly(ADP-ribose) metabolism in p53-regulation and its consequences, Cancer Res, 55, 3697 Shah, 1996, Complete inhibition of poly(ADP-ribose) polymerase activity prevents the recovery of C3H10T1/2 cells from oxidative stress, Biochim Biophys Acta, 1312, 1, 10.1016/0167-4889(96)00004-3 Gaken, 1996, Efficient retroviral infection of mammalian cells is blocked by inhibition of poly(ADP-ribose) polymerase activity, J Virol, 70, 3992, 10.1128/JVI.70.6.3992-4000.1996 Mashima, 1997, Actin cleavage by CPP-32/apopain during the development of apoptosis, Oncogene, 14, 1007, 10.1038/sj.onc.1200919 Kuida, 1996, Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice, Nature, 384, 368, 10.1038/384368a0 Ni, 1997, Cloning and expression of a rat brain interleukin-1β-converting enzyme (ICE)-related protease (IRP) and its possible role in apoptosis of cultured cerebellar granule neurons, J Neurosci, 17, 1561, 10.1523/JNEUROSCI.17-05-01561.1997 Namura, 1998, Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia, J Neurosci, 18, 3659, 10.1523/JNEUROSCI.18-10-03659.1998 Hara, 1997, Inhibition of interleukin 1β converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage, Proc Natl Acad Sci USA, 94, 2007, 10.1073/pnas.94.5.2007 Troy, 1997, Nedd2 is required for apoptosis after trophic factor withdrawal, but not superoxide dismutase (SOD1) downregulation, in sympathetic neurons and PC12 cells, J Neurosci, 17, 1911, 10.1523/JNEUROSCI.17-06-01911.1997 Allet, 1996, Dissecting processing and apoptotic activity of a cysteine protease by mutant analysis, J Cell Biol, 135, 479, 10.1083/jcb.135.2.479 Gu, 1995, Cleavage of poly(ADP-ribose) polymerase by interleukin-1 beta converting enzyme and its homologs TX and Nedd-2, J Biol Chem, 270, 18715, 10.1074/jbc.270.32.18715 Srinivasan, 1996, Bcl-2 expression in neural cells blocks activation of ICE/CED-3 family proteases during apoptosis, J Neurosci, 16, 5654, 10.1523/JNEUROSCI.16-18-05654.1996 Henderson, 1993, Epstein–Barr virus-encoded BHRF1 protein, a viral homolgue of Bcl-2, protects human B cells from programmed cell death, Proc Natl Acad Sci USA, 90, 8479, 10.1073/pnas.90.18.8479 Lam, 1994, Evidence that Bcl-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes, Proc Natl Acad Sci USA, 91, 6569, 10.1073/pnas.91.14.6569 Antonsson, 1997, Inhibition of Bax channel-forming activity by Bcl-2, Science, 277, 370, 10.1126/science.277.5324.370 Antonsson, 2000, Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome-c release from mitochondria, Biochem J, 345, 271, 10.1042/0264-6021:3450271 Snider, 1999, Apoptosis and necrosis in cerebrovascular disease, Ann New York Acad Sci, 893, 243, 10.1111/j.1749-6632.1999.tb07829.x Zha, 1996, Serine phosphorylation of death agonist BAD in response to survival factor results in binding 14-3-3 not Bcl-Xl, Cell, 87, 619, 10.1016/S0092-8674(00)81382-3 Datta, 1997, Akt phosphorylation of Bad couples survival signals to the cell intrinsic death machinery, Cell, 91, 231, 10.1016/S0092-8674(00)80405-5 Kennedy, 1999, Akt/protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria, Mol Cell Biol, 19, 5800, 10.1128/MCB.19.8.5800 Wang, 1999, Ca2+-induced apoptosis through calcineurin dephosphorylation of Bad, Science, 284, 339, 10.1126/science.284.5412.339 Srivastava, 1998, Phosphorylation of eukaryotic translation initiation factor 2 mediates apoptosis in response to activation of the double-stranded RNA-dependent protein kinase, J Biol Chem, 273, 2416, 10.1074/jbc.273.4.2416 Gil, 1999, Induction of apoptosis by double-stranded-RNA-dependent protein kinase (PKR) involves the alpha subunit of eukaryotic translation initiation factor 2 and NF-κB, Mol Cell Biol, 19, 4653, 10.1128/MCB.19.7.4653 Kaufman RJ, Kumar KU, Wu S, Srivastava SP. Regulation of the double-stranded RNA-dependent protein kinase (PKR) and its role in apoptosis. Translational control. Cold Spring Harbor Laboratories, 1998:330. Kohno, 1997, Neuroprotective nitric oxide synthase inhibitor reduces intracellular calcium accumulation following transient global ischemia in gerbil, Neurosci Lett, 224, 17, 10.1016/S0304-3940(97)13459-0 Sharp, 1993, Differential immunohistochemical localization of inositol 1,4,5-trisphosphate- and ryanodine-sensitive Ca2+ release channels in rat brain, J Neurosci, 13, 3051, 10.1523/JNEUROSCI.13-07-03051.1993 Uehara, 1996, Modulation of ryanodine binding to the cardiac Ca2+ release channel by arachidonic acid, J Mol Cell Cardiol, 18, 43, 10.1006/jmcc.1996.0005 Marks, 1997, Intracellular calcium-release channels: regulators of cell life and death, Am J Physiol, 272, H597 Marks, 1996, Cellular functions of immunophilins, Physiol Rev, 76, 631, 10.1152/physrev.1996.76.3.631 Cameron, 1995, Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux, Proc Natl Acad Sci USA, 92, 1784, 10.1073/pnas.92.5.1784 Timermann, 1995, Characterization of an exchange reaction between soluble FKBP-12 and the FKBP–ryanodine receptor complex. Modulation by FKBP mutants deficient in peptidyl-prolyl isomerase activity, J Biol Chem, 270, 2451, 10.1074/jbc.270.6.2451 Sharkey, 1994, Immunophilins mediate the neuroprotective effects of FK506 in focal cerebral ischemia, Nature, 371, 336, 10.1038/371336a0 Katayama, 1997, Immunosuppressant FK506 enhances immediate-early gene expression and prevents delayed neuronal death in the gerbil hippocampus, J Cereb Blood Flow Metab, 17, S492 Kamlya, 1997, Neuroprotective effects of immunosuppressant FK506 in focal cerebral ischemia in the rat: the effect on cerebral infarction, brain edema, immediate-early genes, and heat shock protein hsp72, J Cereb Blood Flow Metab, 17, S372 Thomson, 1995, Mode of action of tacrolimus (FK506): molecular and cellular mechanisms, Ther Drug Monit, 17, 584, 10.1097/00007691-199512000-00007 Bierer, 1991, The effect of the immunosuppressant FK-506 on alternate pathways of T cell activation, Eur J Immunol, 21, 439, 10.1002/eji.1830210228 Odom, 1997, The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein, Antimicrob Agents Chemother, 41, 156, 10.1128/AAC.41.1.156 Fischer, 1993, A mechanism for rotamase catalysis by the FK506 binding protein (FKBP), Biochemistry, 32, 13830, 10.1021/bi00213a011 Galat, 1993, Peptidylproline cis–trans-isomerases: immunophilins, Eur J Biochem, 216, 689, 10.1111/j.1432-1033.1993.tb18189.x Montague, 1997, Native recombinant cyclophilins A, B, and C degrade DNA independently of peptidylprolyl cis–trans-isomerase activity. Potential roles of cyclophilins in apoptosis, J Biol Chem, 272, 6677, 10.1074/jbc.272.10.6677 Montague, 1994, The calcium-dependent nuclease from apoptotic rat thymocytes is homologous with cyclophilin. Recombinant cyclophilins A, B, and C have nuclease activity, J Biol Chem, 169, 18877, 10.1016/S0021-9258(17)32249-4 Wine, 1997, Cyclophilin A is present in rat germ cells and is associated with spermatocyte apoptosis, Biol Reprod, 56, 439, 10.1095/biolreprod56.2.439 Fraser, 1996, Endo-exonuclease of human leukaemic cells: evidence for a role in apoptosis, J Cell Sci, 109, 2343, 10.1242/jcs.109.9.2343 Hughes, 1999, Potassium is a critical regulator of apoptotic enzymes in vitro and in vivo, Adv Enzyme Regul, 39, 157, 10.1016/S0065-2571(98)00010-7 Sakahira, 1999, Functional differences of two forms of the inhibitor of caspase-activated DNAse, ICAD-L, and ICAD-S, J Biol Chem, 274, 15740, 10.1074/jbc.274.22.15740 Tanveer, 1996, Involvement of cyclophilin D in the activation of a mitochondrial pore by Ca2+ and oxidant stress, Eur J Biochem, 238, 166, 10.1111/j.1432-1033.1996.0166q.x Andreeva, 1995, Evidence for involvement of a membrane-associated cyclosporin-A binding protein in the Ca2+-activated inner membrane pore of heart mitochondria, Eur J Biochem, 230, 1125, 10.1111/j.1432-1033.1995.tb20664.x Schweizer, 1993, Sensitivity of mitochondrial peptidyl-prolyl cis–trans isomerase, pyridine nucleotide hydrolysis, and Ca2+ release to cyclosporin A and related compounds, Biochem Pharmacol, 45, 641, 10.1016/0006-2952(93)90138-M Liu, 1992, Inhibition of T cell signaling by immunophilin–ligand complexes correlates with loss of calcineurin phosphatase activity, Biochemistry, 31, 3896, 10.1021/bi00131a002 Dawson, 1993, Immunosuppressant FK506 enhances phosphorylation of nitric oxide synthase and protects against glutamate neurotoxicity, Proc Natl Acad Sci USA, 90, 9808, 10.1073/pnas.90.21.9808 Wiederrecht, 1992, Characterization of high molecular weight FK-506 binding activities reveals a novel FK-506 binding protein as well as a protein complex, J Biol Chem, 267, 21753, 10.1016/S0021-9258(19)36676-1 Steiner, 1997, Neurotrophic actions of nonimmunosuppressive analogues of immunosuppressive drugs FK506, rapamycin and cyclosporin A, Nat Med, 3, 421, 10.1038/nm0497-421 Toung, 1999, Neuroprotective FK506 does not alter in vivo nitric oxide production during ischemia and early reperfusion in rats, Stroke, 30, 1279, 10.1161/01.STR.30.6.1279 Schuler, 2000, p53 induces apoptosis by caspase activation through mitochondrial cytochrome-c release, J Biol Chem, 275, 7337, 10.1074/jbc.275.10.7337 Larsson, 1987, Drastically increased expression of myc and fos proto-oncogenes during in vitro differentiation of chronic lymphocytic cells, Proc Natl Acad Sci USA, 84, 223, 10.1073/pnas.84.1.223 Sheng, 1990, The regulation and function of c-fos and other immediate early genes in the nervous system, Neuron, 4, 477, 10.1016/0896-6273(90)90106-P Angel, 1991, The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation, Biochim Biophys Acta, 1072, 129 Ransone, 1993, The bZIP domains of Fos and Jun mediate a physical association with the TATA box-binding protein, Gene Expr, 3, 37 Uemura, 1991, Global ischemia induces NMDA receptor-mediated c-fos expression in neurons resistant to injury in gerbil hippocampus, Brain Res, 542, 343, 10.1016/0006-8993(91)91589-S Wessel, 1991, In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia, Brain Res, 567, 231, 10.1016/0006-8993(91)90800-B Jorgensen, 1989, Delayed c-fos proto-oncogene expression in the rat hippocampus induced by transient global ischemia: an in situ hybridization study, Brain Res, 484, 393, 10.1016/0006-8993(89)90388-0 Uemura, 1991, Focal ischemia in rats causes time-dependent expression of c-Fos immunoreactivity in widespread regions of ipsilateral cortex, Brain Res, 552, 99, 10.1016/0006-8993(91)90665-I Jorgensen, 1991, Post-ischemic and kanic acid-induced c-Fos protein expression in the rat hippocampus, Acta Neurol Scand, 84, 352, 10.1111/j.1600-0404.1991.tb04968.x Zhang, 1999, Suppression of post-ischemic-induced FOS protein expression by an antisense oligonucleotide to c-fos mRNA leads to increased tissue damage, Brain Res, 832, 112, 10.1016/S0006-8993(99)01459-6 Schiaffonati, 1990, Reprogramming of gene expression in post-ischemic rat liver: induction of proto-oncogenes and hsp-70 gene family, J Cell Physiol, 143, 79, 10.1002/jcp.1041430110 Pelham, 1986, Speculations on the functions of the major heat shock proteins and glucose regulated proteins, Cell, 46, 959, 10.1016/0092-8674(86)90693-8 Beckmann, 1990, Interaction of HSP-70 with newly synthesized proteins: implications for protein folding and assembly, Science, 248, 850, 10.1126/science.2188360 Hightower, 1991, Heat shock, stress proteins, chaperones, and proteotoxicity, Cell, 66, 191, 10.1016/0092-8674(91)90611-2 Schlesinger, 1986, Heat shock proteins: the search for functions, J Cell Biol, 103, 321, 10.1083/jcb.103.2.321 Deshaies, 1988, The role of stress proteins in membrane biogenesis, TIBS, 13, 384 Burdon, 1986, Heat shock and heat shock proteins, J Biochem, 240, 313, 10.1042/bj2400313 Rordorf, 1991, Heat shock protects cultured neurons from glutamate toxicity, Neuron, 7, 1043, 10.1016/0896-6273(91)90348-4 Ting, 1989, Insulin-induced expression of human heat shock protein gene hsp-70, J Biol Chem, 264, 3404, 10.1016/S0021-9258(18)94081-0 Nowak, 1991, Localization of 70 kDa stress protein mRNA induction in gerbil brain after ischemia, J Cereb Blood Flow Metab, 11, 432, 10.1038/jcbfm.1991.84 Nowak, 1985, Synthesis of a stress protein following transient ischemia in the gerbil, J Neurochem, 45, 1635, 10.1111/j.1471-4159.1985.tb07236.x Gonzalez, 1991, Induction of heat shock protein 72-like immunoreactivity in the hippocampal formation following transient global ischemia, Brain Res Bull, 26, 241, 10.1016/0361-9230(91)90234-B Vass, 1988, Localization of 70 kDa stress protein induction in gerbil brain after ischemia, Acta Neuropathol (Berlin), 77, 128, 10.1007/BF00687422 Higo, 1989, Elevated expression of proto-oncogenes accompany enhanced induction of heat-shock genes after exposure of rat embryos in utero to ionizing radiation, Teratog Carcinog Mutag, 9, 191, 10.1002/tcm.1770090402 Privalle, 1987, Induction of superoxide dismutase in E. coli by heat shock, Proc Natl Acad Sci USA, 84, 2723, 10.1073/pnas.84.9.2723 Drummond, 1986, Large changes in intracellular pH and calcium observed during heat shock are not responsible for the induction of heat shock proteins in Drosophila melanogaster, Mol Cell Biol, 6, 1767, 10.1128/MCB.6.5.1767 Urano, 2000, Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1, Science, 287, 664, 10.1126/science.287.5453.664 Behrens, 1999, Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation, Nat Genet, 21, 326, 10.1038/6854 Herdegen, 1998, Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal kinases after neuronal injury, J Neurochem, 18, 5124 Xanthoudakis, 1992, Redox activation of Fos–Jun DNA binding is mediated by a DNA repair enzyme, EMBO J, 11, 3323, 10.1002/j.1460-2075.1992.tb05411.x Xanthoudakis, 1994, The redox and DNA-repair activities of Ref-1 are encoded by non-overlapping domains, Proc Natl Acad Sci USA, 91, 23, 10.1073/pnas.91.1.23 Zinszner, 1998, CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum, Genes Dev, 12, 982, 10.1101/gad.12.7.982 Ubeda, 1999, CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins, Mol Cell Biol, 19, 7589, 10.1128/MCB.19.11.7589 White, 1996, Global brain ischemia and reperfusion, Ann Emerg Med, 27, 588, 10.1016/S0196-0644(96)70161-0 The control of cell proliferation. In: Watson JD, Hopkins NH, Roberts JW, Stietz JA, Weiner AM, editors. Molecular biology of the gene. 4th ed. Menlo Park, CA: Benjamin/Cummings, 1987:962–92. McKay, 1990, Mechanisms regulating cell number and type in the mammalian central nervous system, Cold Spring Harbor Symp Quant Biol, 55, 291, 10.1101/SQB.1990.055.01.031 Cattaneo, 1990, Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor, Nature, 347, 762, 10.1038/347762a0 Havarankova, 1978, Insulin receptors are widely distributed in the central nervous system of the rat, Nature, 272, 827, 10.1038/272827a0 Werther, 1987, Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry, Endocrinology, 121, 1562, 10.1210/endo-121-4-1562 Hill, 1986, Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas, Neuroscience, 17, 1127, 10.1016/0306-4522(86)90082-5 Wanaka, 1990, Localization of FGF receptor mRNA in the adult rat central nervous system by in situ hybridization, Neuron, 5, 267, 10.1016/0896-6273(90)90164-B Cheng, 1991, NGF and β-FGF protect rat hippocampal and human cortical neurons against hypoglycemic damage by stabilizing calcium homeostasis, Neuron, 7, 1031, 10.1016/0896-6273(91)90347-3 Taniuchi, 1986, Nerve growth factor receptor molecules in rat brain, Proc Natl Acad Sci USA, 83, 1950, 10.1073/pnas.83.6.1950 Koh, 1989, Localization of nerve growth factor receptor messenger RNA and protein in the adult rat brain, Exp Neurol, 106, 209, 10.1016/0014-4886(89)90154-4 Unsicker, 1991, Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system, Neuroscience, 44, 613, 10.1016/0306-4522(91)90082-Y Marks, 1991, Localization of type I insulin-like growth factor receptor messenger RNA in the adult rat brain by in situ hybridization, Mol Endocrinol, 5, 1158, 10.1210/mend-5-8-1158 Knusel, 1991, Trophic actions of IGF-I, IGF-II and insulin on cholinergic and dopaminergic brain neurons, Adv Exp Med Biol, 293, 351, 10.1007/978-1-4684-5949-4_31 Lauterio, 1991, Regulation and physiological function of insulin-like growth factors in the central nervous system, Adv Exp Med Biol, 293, 419, 10.1007/978-1-4684-5949-4_37 Breese, 1991, Distribution of insulin-like growth factor 1 (IGF-1) and 2 (IGF-2) receptors in the hippocampal formation of rats and mice, Adv Exp Med Biol, 293, 449, 10.1007/978-1-4684-5949-4_40 Marks, 1991, Localization of insulin and type 1 IGF receptors in rat brain by in vitro autoradiography and in situ hybridization, Adv Exp Med Biol, 293, 459, 10.1007/978-1-4684-5949-4_41 Plata-Salaman, 1991, Epidermal growth factor and the nervous system, Peptides, 12, 653, 10.1016/0196-9781(91)90115-6 Kiyota, 1991, Increase in basic fibroblast growth factor-like immunoreactivity in rat brain after forebrain ischemia, Brain Res, 545, 322, 10.1016/0006-8993(91)91307-M Gluckman, 1992, A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury, Biochem Biophys Res Commun, 182, 593, 10.1016/0006-291X(92)91774-K Varon, 1991, Nerve growth factor in CNS repair and regeneration, Adv Exp Med Biol, 296, 267, 10.1007/978-1-4684-8047-4_25 Mattson, 1989, Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture, J Neurosci, 9, 3728, 10.1523/JNEUROSCI.09-11-03728.1989 Shigeno, 1991, Amelioration of delayed neuronal death in the hippocampus by nerve growth factor, J Neurosci, 11, 2914, 10.1523/JNEUROSCI.11-09-02914.1991 Voll, 1991, Post-ischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of post-ischemic diazepam and insulin, Neurology, 41, 423, 10.1212/WNL.41.3.423 LeMay, 1988, Insulin administration protects neurological function in cerebral ischemia in rats, Stroke, 19, 1411, 10.1161/01.STR.19.11.1411 Standaert, 1988, Insulin-glycerolipid mediators and gene expression, FASEB J, 2, 2453, 10.1096/fasebj.2.9.3286349 Farese, 1987, Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis, Science, 236, 586, 10.1126/science.3107122 Yarden, 1988, Growth factor receptor tyrosine kinases, Annu Rev Biochem, 57, 443, 10.1146/annurev.bi.57.070188.002303 Pillion, 1992, Insulin signal transduction: the role of protein phosphorylation, Am J Med, 303, 40, 10.1097/00000441-199201000-00009 Sacks, 1989, Tyrosine-specific phosphorylation of calmodulin by the insulin receptor kinase purified from human placenta, Biochem J, 263, 803, 10.1042/bj2630803 Laurino, 1988, The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase, Arch Biochem Biophys, 265, 8, 10.1016/0003-9861(88)90365-7 Moss, 1990, Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor, Proc Natl Acad Sci USA, 87, 4453, 10.1073/pnas.87.12.4453 Lee-Kwon, 1998, Antiapoptotic signaling by the insulin receptor in chinese hamster ovary cells, Biochemistry, 37, 15747, 10.1021/bi9805947 Bertrand, 1998, A role for nuclear factor κB in the antiapoptotic function of insulin, J Biol Chem, 273, 2931, 10.1074/jbc.273.5.2931 Kulik, 1997, Antiapoptotic signalling by the insulin-like growth factor 1 receptor, phosphatidylinositol 3-kinase, and Akt, Mol Cell Biol, 17, 1595, 10.1128/MCB.17.3.1595 Parrizas, 1997, Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3′-kinase and mitogen-activated protein kinase pathways, J Biol Chem, 272, 154, 10.1074/jbc.272.1.154 Bertrand, 1999, Insulin antiapoptotic signaling involves insulin activation of the nuclear factor κB-dependent survival genes encoding tumor necrosis factor receptor-associated factor 2 and manganese-superoxide dismutase, J Biol Chem, 274, 30596, 10.1074/jbc.274.43.30596 Gonzalez-Zulueta, 2000, Requirement for nitric oxide activation of p21ras/extracellular regulated kinase in neuronal ischemic preconditioning, Proc Natl Acad Sci, 97, 436, 10.1073/pnas.97.1.436 Teng, 1999, Activation of c-Ha-Ras by nitric oxide modulates survival responsiveness in neuronal PC12 cells, J Biol Chem, 274, 37315, 10.1074/jbc.274.52.37315 Kim, 1999, Disruption of the mouse Rce-1 gene results in defective ras processing and mislocalization of Ras within cells, J Biol Chem, 274, 8383, 10.1074/jbc.274.13.8383 Goalstone, 1998, Effect of insulin on farnesyltransferase. Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor, J Biol Chem, 273, 23892, 10.1074/jbc.273.37.23892 Nobutaka, 1998, Farnesyltransferase inhibitors induce cytochrome-c release and caspase 3 activation preferentially in transformed cells, Proc Natl Acad Sci USA, 95, 15356, 10.1073/pnas.95.26.15356 Strong, 1998, The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus, EMBO J, 17, 3351, 10.1093/emboj/17.12.3351 Kawsome, 1998, Targeted disruption of p70s6k defines its role in protein synthesis and rapamycin sensitivity, Proc Natl Acad Sci USA, 95, 5033, 10.1073/pnas.95.9.5033 Welsh, 1998, Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin, FEBS Lett, 421, 125, 10.1016/S0014-5793(97)01548-2 Law, 1999, Inhibition of DNA synthesis by a farnesyltransferase inhibitor involves inhibition of the p70s6k pathway, J Biol Chem, 274, 4743, 10.1074/jbc.274.8.4743 DeLuca, 1999, Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes, Am J Physiol, 276, H1520 Jiang, 2000, The phosphoinositide 3-OH kinase/AKT2 pathway is a critical target for farnesyltransferase inhibitor-induced apoptosis, Mol Cell Biol, 20, 139, 10.1128/MCB.20.1.139-148.2000 Heck, 1999, Insulin-like growth factor-1-mediated neuroprotection against oxidative stress is associated with activation of nuclear factor κB, J Biol Chem, 274, 9828, 10.1074/jbc.274.14.9828 Kaliman, 1999, Insulin-like growth factor-II, phosphatidylinositol 3-kinase, nuclear factor-kappaB and inducible nitric-oxide synthase define a common myogenic signaling pathway, J Biol Chem, 274, 17437, 10.1074/jbc.274.25.17437 Philpott, 1997, Activated phosphatidylinositol 3-kinase and Akt promote survival of superior cervical neurons, J Cell Biol, 139, 809, 10.1083/jcb.139.3.809 Xue, 2000, The Ras/phosphatidylinositol 3-kinase and Ras/ERK pathways function as independent survival modules each of which inhibits a distinct apoptotic signaling pathway in sympathetic neurons, J Biol Chem, 275, 8817, 10.1074/jbc.275.12.8817 Dufner, 1999, Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation, Mol Cell Biol, 19, 4525, 10.1128/MCB.19.6.4525 Staal, 1987, Molecular cloning of the akt oncogene and its human homologs Akt1 and Akt2: amplification of Akt1 in a primary human gastric adenocarcinoma, Proc Natl Acad Sci USA, 84, 5034, 10.1073/pnas.84.14.5034 Cardone, 1998, Regulation of cell death protease caspase-9 by phosphorylation, Science, 282, 1318, 10.1126/science.282.5392.1318 Brunet, 1999, Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor, Cell, 96, 857, 10.1016/S0092-8674(00)80595-4 Biggs, 1999, Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1, Proc Natl Acad Sci USA, 96, 7421, 10.1073/pnas.96.13.7421 Ozes, 1999, NF-κB activation by tumor necrosis factor requires the Akt serine-threonine kinase, Nature, 401, 82, 10.1038/43466 Madrid, 2000, Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-κB, Mol Cell Biol, 20, 1626, 10.1128/MCB.20.5.1626-1638.2000 Mendez, 1996, Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-1 phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase, Mol Cell Biol, 16, 2857, 10.1128/MCB.16.6.2857 Van Weeren, 1998, Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative PKB, Biol Chem, 273, 13150, 10.1074/jbc.273.21.13150 Quevedo, 2000, Two different signal transduction pathways are implicated in the regulation of initiation factor 2B activity in insulin-like growth factor-1-stimulated neuronal cells, J Biol Chem, 275, 19192, 10.1074/jbc.M000238200 Widmann, 1998, Caspase-dependent cleavage of signaling proteins during apoptosis: a turn-off mechanism for anti-apoptotic signals, J Biol Chem, 273, 7141, 10.1074/jbc.273.12.7141 Drews, 1990, Galanin and epinephrine act on distinct receptors to inhibit insulin release by the same mechanisms, including an increase in K+ permeability of the β-cell membrane, Endocrinology, 126, 1646, 10.1210/endo-126-3-1646 Yu, 1985, Regulation of insulin receptor kinase by multisite phosphorylation, Biochimie, 67, 1081, 10.1016/S0300-9084(85)80105-X Sotomatsu, 1990, Phospholipid peroxidation induced by the catechol–Fe3+(Cu2+) complex: a possible mechanism of nigrostriatal cell damage, Arch Biochem Biophys, 283, 334, 10.1016/0003-9861(90)90651-E Iwahashi, 1989, Enhancement by catechols of hydroxyl-radical formation in the presence of ferric ions and hydrogen peroxide, J Biochem, 105, 429, 10.1093/oxfordjournals.jbchem.a122681 Tanaka, 1991, Dopa and dopamine cause cultured neuronal death in the presence of iron, J Neurol Sci, 101, 198, 10.1016/0022-510X(91)90046-A Tirosh, 1999, Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes, J Biol Chem, 274, 10595, 10.1074/jbc.274.15.10595