Principles for integrating reactive species into in vivo biological processes: Examples from exercise physiology

Affourtit, 2015, On the mechanism by which dietary nitrate improves human skeletal muscle function, Front. Physiol., 6, 211, 10.3389/fphys.2015.00211 Albrecht, 2011, In vivo mapping of hydrogen peroxide and oxidized glutathione reveals chemical and regional specificity of redox homeostasis, Cell Metab., 14, 819, 10.1016/j.cmet.2011.10.010 Altenhöfer, 2012, The NOX toolbox: validating the role of NADPH oxidases in physiology and disease, Cell. Mol. Life Sci., 69, 2327, 10.1007/s00018-012-1010-9 Anderson, 2009, Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans, J. Clin. Invest., 119, 573, 10.1172/JCI37048 Andrade, 1998, Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse, J. Physiol., 509, 565, 10.1111/j.1469-7793.1998.565bn.x Aon-Bertolino, 2011, Thioredoxin and glutaredoxin system proteins-immunolocalization in the rat central nervous system, Biochim. Biophys. Acta, 1810, 93, 10.1016/j.bbagen.2010.06.011 Arnold, 2002, PARP-mediated proteasome activation: a co-ordination of DNA repair and protein degradation?, BioEssays, 24, 1060, 10.1002/bies.10179 Augusto, 2002, Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology, Free Radic. Biol. Med., 32, 841, 10.1016/S0891-5849(02)00786-4 Baez, 2015, Mass spectrometry in studies of protein thiol chemistry and signaling: opportunities and caveats, Free Radic. Biol. Med., 80, 191, 10.1016/j.freeradbiomed.2014.09.016 Bailey, 2004, Regulation of free radical outflow from an isolated muscle bed in exercising humans, Am. J. Physiol. Heart Circ. Physiol., 287, H1689, 10.1152/ajpheart.00148.2004 Balon, 1994, Nitric oxide release is present from incubated skeletal muscle preparations, J. Appl. Physiol. (1985), 77, 2519, 10.1152/jappl.1994.77.6.2519 Beltrán, 2000, Oxidative stress and S-nitrosylation of proteins in cells, Br. J. Pharmacol., 129, 953, 10.1038/sj.bjp.0703147 Belousov, 2006, Genetically encoded fluorescent indicator for intracellular hydrogen peroxide, Nat. Methods, 3, 281, 10.1038/nmeth866 Benhar, 2009, Protein denitrosylation: enzymatic mechanisms and cellular functions, Nat. Rev. Mol. Cell Biol., 10, 721, 10.1038/nrm2764 Benhar, 2008, Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins, Science, 320, 1050, 10.1126/science.1158265 Berndt, 2014, Redox regulation by glutathione needs enzymes, Front. Pharmacol., 5, 168, 10.3389/fphar.2014.00168 Biteau, 2003, ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin, Nature, 425, 980, 10.1038/nature02075 Bleier, 2015, Generator-specific targets of mitochondrial reactive oxygen species, Free Radic. Biol. Med., 78, 1, 10.1016/j.freeradbiomed.2014.10.511 Block, 2009, Subcellular localization of Nox4 and regulation in diabetes, Proc. Natl. Acad. Sci. U. S. A., 106, 14385, 10.1073/pnas.0906805106 Braakhuis, 2015, Impact of dietary antioxidants on sport performance: a review, Sports Med., 45, 939, 10.1007/s40279-015-0323-x Brandes, 2014, Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases, J. Mol. Cell. Cardiol., 73, 70, 10.1016/j.yjmcc.2014.02.006 Brewer, 2015, Chemical approaches to discovery and study of sources and targets of hydrogen peroxide redox signaling through NADPH oxidase proteins, Annu. Rev. Biochem., 84, 765, 10.1146/annurev-biochem-060614-034018 Brigelius-Flohé, 2011, Basic principles and emerging concepts in the redox control of transcription factors, Antioxid. Redox Signal., 15, 2335, 10.1089/ars.2010.3534 Brot, 1983, Biochemistry and physiological role of methionine sulfoxide residues in proteins, Arch. Biochem. Biophys., 223, 271, 10.1016/0003-9861(83)90592-1 Brown, 2012, There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells, Mitochondrion, 12, 1, 10.1016/j.mito.2011.02.001 Buettner, 2015, Moving free radical and redox biology ahead in the next decade(s), Free Radic. Biol. Med., 78, 236, 10.1016/j.freeradbiomed.2014.10.578 Buettner, 2011, Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide, Anti Cancer Agents Med. Chem., 11, 341, 10.2174/187152011795677544 Carballal, 2014, Kinetic and mechanistic considerations to assess the biological fate of peroxynitrite, Biochim. Biophys. Acta, 1840, 768, 10.1016/j.bbagen.2013.07.005 Cardaci, 2012, Redox implications of AMPK-mediated signal transduction beyond energetic clues, J. Cell Sci., 125, 2115, 10.1242/jcs.095216 Castro, 2012, Carbonylation of the cytoskeletal protein actin leads to aggregate formation, Free Radic. Biol. Med., 53, 916, 10.1016/j.freeradbiomed.2012.06.005 Catalgol, 2010, Chromatin repair after oxidative stress: role of PARP-mediated proteasome activation, Free Radic. Biol. Med., 48, 673, 10.1016/j.freeradbiomed.2009.12.010 Chang, 2004, Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine, J. Biol. Chem., 279, 50994, 10.1074/jbc.M409482200 Chen, 2009, Superoxide is the major reactive oxygen species regulating autophagy, Cell Death Differ., 16, 1040, 10.1038/cdd.2009.49 Cheng, 2011, Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway, Antioxid. Redox Signal., 14, 469, 10.1089/ars.2010.3283 Chondrogianni, 2014, Protein damage, repair and proteolysis, Mol. Asp. Med., 35, 1, 10.1016/j.mam.2012.09.001 Close, 2014, Antioxidants and exercise: a tale of the complexities of relating signalling processes to physiological function?, J. Physiol., 592, 1721, 10.1113/jphysiol.2014.272294 Close, 2005, Microdialysis studies of extracellular reactive oxygen species in skeletal muscle: factors influencing the reduction of cytochrome c and hydroxylation of salicylate, Free Radic. Biol. Med., 39, 1460, 10.1016/j.freeradbiomed.2005.07.009 Cobley, 2015, Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations, Free Radic. Biol. Med., 84, 65, 10.1016/j.freeradbiomed.2015.03.018 Cobley, 2015, The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay, Front. Physiol., 6, 182, 10.3389/fphys.2015.00182 Cobley, 2015, Exercise improves mitochondrial and redox-regulated stress responses in the elderly: better late than never!, Biogerontology, 16, 249, 10.1007/s10522-014-9546-8 Cobley, 2014, Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle, Free Radic. Biol. Med., 70, 23, 10.1016/j.freeradbiomed.2014.02.004 Cobley, 2011, N-Acetylcysteine's attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations, Int. J. Sport Nutr. Exerc. Metab., 21, 451, 10.1123/ijsnem.21.6.451 Cochemé, 2011, Measurement of H2O2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix, Cell Metab., 13, 340, 10.1016/j.cmet.2011.02.003 Collins, 2012, Mitochondrial redox signalling at a glance, J. Cell Sci., 125, 801, 10.1242/jcs.098475 Costantini, 2014 Costill, 1992, Carbohydrate nutrition and fatigue, Sports Med., 13, 86, 10.2165/00007256-199213020-00003 D'Autréaux, 2007, ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis, Nat. Rev. Mol. Cell Biol., 8, 813, 10.1038/nrm2256 Dalle-Donne, 2009, Protein S-glutathionylation: a regulatory device from bacteria to humans, Trends Biochem. Sci., 34, 85, 10.1016/j.tibs.2008.11.002 Dammeyer, 2011, Human protein Atlas of redox systems — what can be learnt?, Biochim. Biophys. Acta, 1810, 111, 10.1016/j.bbagen.2010.07.004 Davies, 1982, Free radicals and tissue damage produced by exercise, Biochem. Biophys. Res. Commun., 107, 1198, 10.1016/S0006-291X(82)80124-1 Davison, 2008, In vitro electron paramagnetic resonance characterization of free radicals: relevance to exercise-induced lipid peroxidation and implications of ascorbate prophylaxis, Free Radic. Res., 42, 379, 10.1080/10715760801976618 Dickinson, 2011, Chemistry and biology of reactive oxygen species in signaling or stress responses, Nat. Chem. Biol., 7, 504, 10.1038/nchembio.607 Dickinson, 2008, A targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of living cells, J. Am. Chem. Soc., 130, 9638, 10.1021/ja802355u Dikalov, 2014, Methods for detection of mitochondrial and cellular reactive oxygen species, Antioxid. Redox Signal., 20, 372, 10.1089/ars.2012.4886 Dillard, 1978, Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxidation, J. Appl. Physiol. Respir. Environ. Exerc. Physiol., 45, 927 Doulias, 2013, Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation, Sci. Signal., 6, rs1, 10.1126/scisignal.2003252 Dröge, 2002, Free radicals in the physiological control of cell function, Physiol. Rev., 82, 47, 10.1152/physrev.00018.2001 Dupré, 1995 Dworakowski, 2006, Redox signalling involving NADPH oxidase-derived reactive oxygen species, Biochem. Soc. Trans., 34, 960, 10.1042/BST0340960 Dyson, 2011, An integrated approach to assessing nitroso-redox balance in systemic inflammation, Free Radic. Biol. Med., 51, 1137, 10.1016/j.freeradbiomed.2011.06.012 Eberhardt, 2014, H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway, Nat. Commun., 5, 4381, 10.1038/ncomms5381 Egan, 2013, Exercise metabolism and the molecular regulation of skeletal muscle adaptation, Cell Metab., 17, 162, 10.1016/j.cmet.2012.12.012 Emerling, 2009, Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio, Free Radic. Biol. Med., 46, 1386, 10.1016/j.freeradbiomed.2009.02.019 Espinosa, 2006, Myotube depolarization generates reactive oxygen species through NAD(P)H oxidase; ROS-elicited Ca2+ stimulates ERK, CREB, early genes, J. Cell. Physiol., 209, 379, 10.1002/jcp.20745 Etgen, 1997, Nitric oxide stimulates skeletal muscle glucose transport through a calcium/contraction- and phosphatidylinositol-3-kinase-independent pathway, Diabetes, 46, 1915, 10.2337/diab.46.11.1915 Ferrer-Sueta, 2009, Chemical biology of peroxynitrite: kinetics, diffusion, and radicals, ACS Chem. Biol., 4, 161, 10.1021/cb800279q Fiehn, 1971, Lipids and fatty acids of sarcolemma, sarcoplasmic reticulum, and mitochondria from rat skeletal muscle, J. Biol Chem., 246, 5617, 10.1016/S0021-9258(18)61852-6 Finichiu, 2015, A mitochondria-targeted derivative of ascorbate: MitoC, Free Radic. Biol. Med., 89, 668, 10.1016/j.freeradbiomed.2015.07.160 Forman, 2015, Even free radicals should follow some rules: a guide to free radical research terminology and methodology, Free Radic. Biol. Med., 78, 233, 10.1016/j.freeradbiomed.2014.10.504 Forman, 2014, An overview of mechanisms of redox signaling, J. Mol. Cell. Cardiol., 73, 2, 10.1016/j.yjmcc.2014.01.018 Forman, 2010, Signaling functions of reactive oxygen species, Biochemistry, 49, 835, 10.1021/bi9020378 Forman, 2007, Use and abuse of exogenous H2O2 in studies of signal transduction, Free Radic. Biol. Med., 42, 926, 10.1016/j.freeradbiomed.2007.01.011 Frey, 2008, The radical SAM superfamily, Crit. Rev. Biochem. Mol. Biol., 43, 63, 10.1080/10409230701829169 Giorgio, 2007, Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?, Nat. Rev. Mol. Cell Biol., 8, 722, 10.1038/nrm2240 Giustarini, 2012, N-Acetylcysteine ethyl ester (NACET): a novel lipophilic cell-permeable cysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential, Biochem. Pharmacol., 84, 1522, 10.1016/j.bcp.2012.09.010 Giustarini, 2009, Oxidative stress and human diseases: origin, link, measurement, mechanisms, and biomarkers, Crit. Rev. Clin. Lab. Sci., 46, 241, 10.3109/10408360903142326 Gliemann, 2013, Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men, J. Physiol., 591, 5047, 10.1113/jphysiol.2013.258061 Go, 2015, The cysteine proteome, Free Radic. Biol. Med., 84, 227, 10.1016/j.freeradbiomed.2015.03.022 Go, 2013, The redox proteome, J. Biol. Chem., 288, 26512, 10.1074/jbc.R113.464131 Go, 2011, Protein cysteines map to functional networks according to steady-state level of oxidation, J. Proteomics Bioinform., 4, 196, 10.4172/jpb.1000190 Godoy, 2011, Redox atlas of the mouse. Immunohistochemical detection of glutaredoxin-, peroxiredoxin-, and thioredoxin-family proteins in various tissues of the laboratory mouse, Biochim. Biophys. Acta, 1810, 2, 10.1016/j.bbagen.2010.05.006 Goncalves, 2015, Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise, J. Biol. Chem., 290, 209, 10.1074/jbc.M114.619072 Gomez-Cabrera, 2015, Redox modulation of mitochondriogenesis in exercise. Does antioxidant supplementation blunt the benefits of exercise training?, Free Radic. Biol. Med., 86, 37, 10.1016/j.freeradbiomed.2015.04.006 Gomez-Cabrera, 2010, Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation, Am. J. Physiol. Regul. Integr. Comp. Physiol., 298, R2, 10.1152/ajpregu.00142.2009 Gomez-Cabrera, 2008, Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance, Am. J. Clin. Nutr., 87, 142, 10.1093/ajcn/87.1.142 Gomez-Cabrera, 2005, Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats, J. Physiol., 567, 113, 10.1113/jphysiol.2004.080564 Gould, 2015, Site-specific proteomic mapping identifies selectively modified regulatory cysteine residues in functionally distinct protein networks, Chem. Biol., 22, 965, 10.1016/j.chembiol.2015.06.010 Gould, 2013, Regulation of protein function and signaling by reversible cysteine S-nitrosylation, J. Biol. Chem., 288, 26473, 10.1074/jbc.R113.460261 Hall, 2009, Typical 2-Cys peroxiredoxins—structures, mechanisms and functions, FEBS J., 276, 2469, 10.1111/j.1742-4658.2009.06985.x Halliwell, 2015 Halliwell, 2014, Cell culture, oxidative stress, and antioxidants: avoiding pitfalls, Biomed J., 37, 99 Halliwell, 2013, The antioxidant paradox: less paradoxical now?, Br. J. Clin. Pharmacol., 75, 637, 10.1111/j.1365-2125.2012.04272.x Halliwell, 2012, Free radicals and antioxidants: updating a personal view, Nutr. Rev., 70, 257, 10.1111/j.1753-4887.2012.00476.x Halliwell, 2004, Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?, Br. J. Pharmacol., 142, 231, 10.1038/sj.bjp.0705776 Halliwell, 1987, Oxidants and human disease: some new concepts, FASEB J., 1, 358, 10.1096/fasebj.1.5.2824268 Hancock, 2014, Hydrogen sulfide and cell signaling: team player or referee?, Plant Physiol. Biochem., 78, 37, 10.1016/j.plaphy.2014.02.012 Handayaningsih, 2011, Reactive oxygen species play an essential role in IGF-I signaling and IGF-I-induced myocyte hypertrophy in C2C12 myocytes, Endocrinology, 152, 912, 10.1210/en.2010-0981 Hawley, 2014, Integrative biology of exercise, Cell, 159, 738, 10.1016/j.cell.2014.10.029 Hawley, 1992, Oxidation of carbohydrate ingested during prolonged endurance exercise, Sports Med., 14, 27, 10.2165/00007256-199214010-00003 Hepple, 2003, Aerobic power declines with aging in rat skeletal muscles perfused at matched convective O2 delivery, J. Appl. Physiol. (1985), 94, 744, 10.1152/japplphysiol.00737.2002 Higaki, 2001, Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle, Diabetes, 50, 241, 10.2337/diabetes.50.2.241 Higdon, 2012, The electrophile responsive proteome: integrating proteomics and lipidomics with cellular function, Antioxid. Redox Signal., 17, 1580, 10.1089/ars.2012.4523 Hoffman, 2015, Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates, Cell Metab., 22, 922, 10.1016/j.cmet.2015.09.001 Hogg, 2002, The biochemistry and physiology of S-nitrosothiols, Annu. Rev. Pharmacol. Toxicol., 42, 585, 10.1146/annurev.pharmtox.42.092501.104328 Holmgren, 2010, The use of thiols by ribonucleotide reductase, Free Radic. Biol. Med., 49, 1617, 10.1016/j.freeradbiomed.2010.09.005 Holmström, 2014, Cellular mechanisms and physiological consequences of redox-dependent signalling, Nat. Rev. Mol. Cell Biol., 15, 411, 10.1038/nrm3801 Irrcher, 2009, Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells, Am. J. Physiol. Cell Physiol., 296, C116, 10.1152/ajpcell.00267.2007 Imlay, 2015, Diagnosing oxidative stress in bacteria: not as easy as you might think, Curr. Opin. Microbiol., 24, 124, 10.1016/j.mib.2015.01.004 Imlay, 2013, The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium, Nat. Rev. Microbiol., 11, 443, 10.1038/nrmicro3032 Ito, 2013, Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy, Nat. Med., 19, 101, 10.1038/nm.3019 James, 2005, Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species. Implications for the use of exogenous ubiquinones as therapies and experimental tools, J. Biol. Chem., 280, 21295, 10.1074/jbc.M501527200 Janssen-Heininger, 2008, Redox-based regulation of signal transduction: principles, pitfalls, and promises, Free Radic. Biol. Med., 45, 1, 10.1016/j.freeradbiomed.2008.03.011 Javeshghani, 2002, Molecular characterization of a superoxide-generating NAD(P)H oxidase in the ventilatory muscles, Am. J. Respir. Crit. Care Med., 165, 412, 10.1164/ajrccm.165.3.2103028 Jones, 2015, The Redox Code, Antioxid. Redox Signal., 10.1089/ars.2015.6247 Jones, 2010, Redox sensing: orthogonal control in cell cycle and apoptosis signalling, J. Intern. Med., 268, 432, 10.1111/j.1365-2796.2010.02268.x Jones, 2010, Redox compartmentalization and cellular stress, Diabetes Obes. Metab., 12, 116, 10.1111/j.1463-1326.2010.01266.x Jones, 2008, Radical-free biology of oxidative stress, Am. J. Physiol. Cell Physiol., 295, C849, 10.1152/ajpcell.00283.2008 Jourd'heuil, 2003, Oxidation and nitrosation of thiols at low micromolar exposure to nitric oxide. Evidence for a free radical mechanism, J. Biol. Chem., 278, 15720, 10.1074/jbc.M300203200 Joyner, 2015, Has Neo-Darwinism failed clinical medicine: does systems biology have to?, Prog. Biophys. Mol. Biol., 117, 107, 10.1016/j.pbiomolbio.2014.09.010 Kaludercic, 2014, Reactive oxygen species and redox compartmentalization, Front. Physiol., 5, 285, 10.3389/fphys.2014.00285 Kalyanaraman, 2012, Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations, Free Radic. Biol. Med., 52, 1, 10.1016/j.freeradbiomed.2011.09.030 Kang, 2009, Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling is redox sensitive, Free Radic. Biol. Med., 47, 1394, 10.1016/j.freeradbiomed.2009.08.007 Karagounis, 2009, The 5' adenosine monophosphate-activated protein kinase: regulating the ebb and flow of cellular energetics, Int. J. Biochem. Cell Biol., 41, 2360, 10.1016/j.biocel.2009.07.004 Kelso, 2001, Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties, J. Biol. Chem., 276, 4588, 10.1074/jbc.M009093200 Khawli, 1994, N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro, J. Appl. Physiol., 77, 317, 10.1152/jappl.1994.77.1.317 Kholodenko, 2010, Signalling ballet in space and time, Nat. Rev. Mol. Cell Biol., 11, 414, 10.1038/nrm2901 Kim, 2014, Oxidative stress in angiogenesis and vascular disease, Blood, 123, 625, 10.1182/blood-2013-09-512749 Kobayashi, 2006, Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species, Adv. Enzym. Regul., 46, 113, 10.1016/j.advenzreg.2006.01.007 Kobzik, 1994, Nitric oxide in skeletal muscle, Nature, 372, 546, 10.1038/372546a0 Kohr, 2012, Measurement of S-nitrosylation occupancy in the myocardium with cysteine-reactive tandem mass tags: short communication, Circ. Res., 111, 1308, 10.1161/CIRCRESAHA.112.271320 Kojo, 2012, Oxygen is the key factor associated with the difference between in vivo and in vitro effects of antioxidants, Proc. Natl. Acad. Sci. U. S. A., 109, 10.1073/pnas.1205916109 Krüger, 2009, Exercise affects tissue lymphocyte apoptosis via redox-sensitive and Fas-dependent signaling pathways, Am. J. Physiol. Regul. Integr. Comp. Physiol., 296, R1518, 10.1152/ajpregu.90994.2008 Kubo, 2007, Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: contribution to dual modulation of vascular tension, Toxicology, 232, 138, 10.1016/j.tox.2006.12.023 Kuwahara, 2010, Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy, Free Radic. Biol. Med., 48, 1252, 10.1016/j.freeradbiomed.2010.02.011 Lamb, 2011, Acute effects of reactive oxygen and nitrogen species on the contractile function of skeletal muscle, J. Physiol., 589, 2119, 10.1113/jphysiol.2010.199059 Lee, 2014, Peroxiredoxin 3 has a crucial role in the contractile function of skeletal muscle by regulating mitochondrial homeostasis, Free Radic. Biol. Med., 77, 298, 10.1016/j.freeradbiomed.2014.09.010 Lee, 2011, Mitochondrial H2O2 generated from electron transport chain complex I stimulates muscle differentiation, Cell Res., 21, 817, 10.1038/cr.2011.55 Leonard, 2011, Chemical ‘omics’ approaches for understanding protein cysteine oxidation in biology, Curr. Opin. Chem. Biol., 15, 88, 10.1016/j.cbpa.2010.11.012 Leonard, 2009, Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells, ACS Chem. Biol., 4, 783, 10.1021/cb900105q Leto, 2009, Targeting and regulation of reactive oxygen species generation by Nox family NADPH oxidases, Antioxid. Redox Signal., 11, 2607, 10.1089/ars.2009.2637 Li, 2013, The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells, J. Cell. Mol. Med., 17, 365, 10.1111/jcmm.12016 Li, 2009, GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat, Free Radic. Biol. Med., 47, 103, 10.1016/j.freeradbiomed.2009.04.014 Li, 2008, Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide, Circulation, 117, 2351, 10.1161/CIRCULATIONAHA.107.753467 Liu, 2000, Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants, J. Appl. Physiol., 89, 21, 10.1152/jappl.2000.89.1.21 Lima, 2010, S-nitrosylation in cardiovascular signaling, Circ. Res., 106, 633, 10.1161/CIRCRESAHA.109.207381 Makanae, 2013, Vitamin C administration attenuates overload-induced skeletal muscle hypertrophy in rats, Acta Physiol. (Oxf.), 208, 57, 10.1111/apha.12042 Malik, 2013, Label-free LC–MS profiling of skeletal muscle reveals heart-type fatty acid binding protein as a candidate biomarker of aerobic capacity, Proteome, 1, 290, 10.3390/proteomes1030290 Manda, 2015, The redox biology network in cancer pathophysiology and therapeutics, Redox Biol., 5, 347, 10.1016/j.redox.2015.06.014 Mankowski, 2015, Dietary antioxidants as modifiers of physiologic adaptations to exercise, Med. Sci. Sports Exerc., 47, 1857, 10.1249/MSS.0000000000000620 Margaritelis, 2015, Blood reflects tissue oxidative stress: a systematic review, Biomarkers, 20, 97, 10.3109/1354750X.2014.1002807 Margaritelis, 2014, Reductive stress after exercise: the issue of redox individuality, Redox Biol., 2, 520, 10.1016/j.redox.2014.02.003 Marinho, 2014, Hydrogen peroxide sensing, signaling and regulation of transcription factors, Redox Biol., 2, 535, 10.1016/j.redox.2014.02.006 Marozkina, 2012, S-Nitrosylation signaling regulates cellular protein interactions, Biochim. Biophys. Acta, 1820, 722, 10.1016/j.bbagen.2011.06.017 McConell, 2012, Skeletal muscle nitric oxide signaling and exercise: a focus on glucose metabolism, Am. J. Physiol. Endocrinol. Metab., 303, E301, 10.1152/ajpendo.00667.2011 McDonagh, 2014, Application of redox proteomics to skeletal muscle aging and exercise, Biochem. Soc. Trans., 42, 965, 10.1042/BST20140085 Merry, 2009, Skeletal muscle glucose uptake during exercise: a focus on reactive oxygen species and nitric oxide signaling, IUBMB Life, 61, 479, 10.1002/iub.179 Meyer, 2010, Fluorescent protein-based redox probes, Antioxid. Redox Signal., 13, 621, 10.1089/ars.2009.2948 Michailidis, 2013, Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise, Am. J. Clin. Nutr., 98, 233, 10.3945/ajcn.112.049163 Miller, 2005, Boronate-based fluorescent probes for imaging cellular hydrogen peroxide, J. Am. Chem. Soc., 127, 16652, 10.1021/ja054474f Miranda, 1999, Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells, Biochem. Biophys. Res. Commun., 258, 44, 10.1006/bbrc.1999.0580 Miseta, 2000, Relationship between the occurrence of cysteine in proteins and the complexity of organisms, Mol. Biol. Evol., 17, 1232, 10.1093/oxfordjournals.molbev.a026406 Mishin, 2010, Application of the Amplex red/horseradish peroxidase assay to measure hydrogen peroxide generation by recombinant microsomal enzymes, Free Radic. Biol. Med., 48, 1485, 10.1016/j.freeradbiomed.2010.02.030 Moen, 2014, Redox-sensitive residue in the actin-binding interface of myosin, Biochem. Biophys. Res. Commun., 453, 345, 10.1016/j.bbrc.2014.09.072 Moopanar, 2006, The activity-induced reduction of myofibrillar Ca2+ sensitivity in mouse skeletal muscle is reversed by dithiothreitol, J. Physiol., 571, 191, 10.1113/jphysiol.2005.101105 Morales-Alamo, 2013, Critical role for free radicals on sprint exercise-induced CaMKII and AMPKα phosphorylation in human skeletal muscle, J. Appl. Physiol., 114, 566, 10.1152/japplphysiol.01246.2012 Murrant, 2001, Detection of reactive oxygen and reactive nitrogen species in skeletal muscle, Microsc. Res. Tech., 55, 236, 10.1002/jemt.1173 Murphy, 2014, Signaling by S-nitrosylation in the heart, J. Mol. Cell. Cardiol., 73, 18, 10.1016/j.yjmcc.2014.01.003 Murphy, 2011, Unraveling the biological roles of reactive oxygen species, Cell Metab., 13, 361, 10.1016/j.cmet.2011.03.010 Murphy, 2009, How mitochondria produce reactive oxygen species, Biochem. J., 417, 1, 10.1042/BJ20081386 Murphy, 2007, Targeting antioxidants to mitochondria by conjugation to lipophilic cations, Annu. Rev. Pharmacol. Toxicol., 47, 629, 10.1146/annurev.pharmtox.47.120505.105110 Murphy, 2000, Drug delivery to mitochondria: the key to mitochondrial medicine, Adv. Drug Deliv. Rev., 41, 235, 10.1016/S0169-409X(99)00069-1 Neubauer, 2015, Antioxidants in athlete’s basic nutrition: considerations towards a guideline for the intake of vitamin C and vitamin E Niki, 2009, Lipid peroxidation: physiological levels and dual biological effects, Free Radic. Biol. Med., 47, 469, 10.1016/j.freeradbiomed.2009.05.032 Nikolaidis, 2015, Common questions and tentative answers on how to assess oxidative stress after antioxidant supplementation and exercise Nikolaidis, 2012, Redox biology of exercise: an integrative and comparative consideration of some overlooked issues, J. Exp. Biol., 215, 1615, 10.1242/jeb.067470 Nikolaidis, 2012, Does vitamin C and E supplementation impair the favorable adaptations of regular exercise?, Oxidative Med. Cell. Longev., 2012, 707941, 10.1155/2012/707941 Nikolaidis, 2012, Exercise as a model to study redox homeostasis in blood: the effect of protocol and sampling point, Biomarkers, 17, 28, 10.3109/1354750X.2011.635805 Nikolaidis, 2011, F2-isoprostane formation, measurement and interpretation: the role of exercise, Prog. Lipid Res., 50, 89, 10.1016/j.plipres.2010.10.002 Nikolaidis, 2009, Blood as a reactive species generator and redox status regulator during exercise, Arch. Biochem. Biophys., 490, 77, 10.1016/j.abb.2009.08.015 Osterburg, 2013, Concerns over interspecies transcriptional comparisons in mice and humans after trauma, Proc. Natl. Acad. Sci. U. S. A., 110, E 3370, 10.1073/pnas.1306033110 Palomero, 2012, Effect of passive stretch on intracellular nitric oxide and superoxide activities in single skeletal muscle fibres: influence of ageing, Free Radic. Res., 46, 30, 10.3109/10715762.2011.637203 Palomero, 2008, In situ detection and measurement of intracellular reactive oxygen species in single isolated mature skeletal muscle fibers by real time fluorescence microscopy, Antioxid. Redox Signal., 10, 1463, 10.1089/ars.2007.2009 Papin, 2004, Hierarchical thinking in network biology: the unbiased modularization of biochemical networks, Trends Biochem. Sci., 29, 641, 10.1016/j.tibs.2004.10.001 Paschalis, 2014, Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation, Eur. J. Nutr. Patel, 2009, Lipid rafts and caveolae and their role in compartmentation of redox signaling, Antioxid. Redox Signal., 11, 1357, 10.1089/ars.2008.2365 Paulsen, 2014, Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial, J. Physiol., 592, 1887, 10.1113/jphysiol.2013.267419 Peake, 2015, Modulating exercise-induced hormesis: does less equal more?, J. Appl. Physiol. (1985), 119, 172, 10.1152/japplphysiol.01055.2014 Pearson, 2014, Skeletal muscle contractions induce acute changes in cytosolic superoxide, but slower responses in mitochondrial superoxide and cellular hydrogen peroxide, PLoS ONE, 9, 10.1371/journal.pone.0096378 Piantadosi, 2012, Regulation of mitochondrial processes by protein S-nitrosylation, Biochim. Biophys. Acta, 1820, 712, 10.1016/j.bbagen.2011.03.008 Pigliucci, 2003, From molecules to phenotypes? The promise and limits of integrative biology, Basic Appl. Ecol., 4, 297, 10.1078/1439-1791-00161 Place, 2015, Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise, Proc. Natl. Acad. Sci. U. S. A., 10.1073/pnas.1507176112 Poole, 2015, The basics of thiols and cysteines in redox biology and chemistry, Free Radic. Biol. Med., 80, 148, 10.1016/j.freeradbiomed.2014.11.013 Pouvreau, 2014, Genetically encoded reactive oxygen species (ROS) and redox indicators, Biotechnol. J., 9, 282, 10.1002/biot.201300199 Powers, 2011, Exercise-induced oxidative stress in humans: cause and consequences, Free Radic. Biol. Med., 51, 942, 10.1016/j.freeradbiomed.2010.12.009 Quintanilla, 2005, Trolox and 17beta-estradiol protect against amyloid beta-peptide neurotoxicity by a mechanism that involves modulation of the Wnt signaling pathway, J. Biol. Chem., 280, 11615, 10.1074/jbc.M411936200 Radak, 2013, Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling, Antioxid. Redox Signal., 18, 1208, 10.1089/ars.2011.4498 Radak, 2011, Age-associated neurodegeneration and oxidative damage to lipids, proteins and DNA, Mol. Asp. Med., 32, 305, 10.1016/j.mam.2011.10.010 Radak, 2005, Exercise and hormesis: oxidative stress-related adaptation for successful aging, Biogerontology, 6, 71, 10.1007/s10522-004-7386-7 Reczek, 2015, ROS-dependent signal transduction, Curr. Opin. Cell Biol., 33, 8, 10.1016/j.ceb.2014.09.010 Reid, 2015, Redox interventions to increase exercise performance, J. Physiol., 10.1113/JP270653 Reid, 2001, Nitric oxide, reactive oxygen species, and skeletal muscle contraction, Med. Sci. Sports Exerc., 33, 371, 10.1097/00005768-200103000-00006 Reid, 1993, Moody MR. Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle, J. Appl. Physiol. (1985), 75, 1081, 10.1152/jappl.1993.75.3.1081 Reid, 1992, Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro, J. Appl. Physiol. (1985), 73, 1797, 10.1152/jappl.1992.73.5.1797 Reid, 1992, Reactive oxygen in skeletal muscle. II. Extracellular release of free radicals, J. Appl. Physiol. (1985), 73, 1805, 10.1152/jappl.1992.73.5.1805 Reily, 2013, Mitochondrially targeted compounds and their impact on cellular bioenergetics, Redox Biol., 1, 86, 10.1016/j.redox.2012.11.009 Richardson, 2007, Exercise-induced brachial artery vasodilation: role of free radicals, Am. J. Physiol. Heart Circ. Physiol., 292, H1516, 10.1152/ajpheart.01045.2006 Rice, 2012, Animal models: not close enough, Nature, 484, S9, 10.1038/nature11102 Ristow, 2014, Unraveling the truth about antioxidants: mitohormesis explains ROS-induced health benefits, Nat. Med., 20, 709, 10.1038/nm.3624 Ristow, 2009, Antioxidants prevent health-promoting effects of physical exercise in humans, Proc. Natl. Acad. Sci. U. S. A., 106, 8665, 10.1073/pnas.0903485106 Roberts, 1997, Exercise-stimulated glucose transport in skeletal muscle is nitric oxide dependent, Am. J. Phys., 273, E220 Robinson, 2006, Selective fluorescent imaging of superoxide in vivo using ethidium-based probes, Proc. Natl. Acad. Sci. U. S. A., 103, 15038, 10.1073/pnas.0601945103 Rodriguez-Cuenca, 2010, Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice, Free Radic. Biol. Med., 48, 161, 10.1016/j.freeradbiomed.2009.10.039 Roelofs, 2015, Low micromolar concentrations of the superoxide probe MitoSOX uncouple neural mitochondria and inhibit complex IV, Free Radic. Biol. Med., 86, 250, 10.1016/j.freeradbiomed.2015.05.032 Rumora, 2007, Mycotoxin fumonisin B1 alters cellular redox balance and signalling pathways in rat liver and kidney, Toxicology, 242, 31, 10.1016/j.tox.2007.09.006 Sahlin, 2006, Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle, J. Appl. Physiol. (1985), 101, 833, 10.1152/japplphysiol.01007.2005 Saitoh, 1998, Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1, EMBO J., 17, 2596, 10.1093/emboj/17.9.2596 Sakellariou, 2014, Redefining the major contributors to superoxide production in contracting skeletal muscle. The role of NAD(P)H oxidases, Free Radic. Res., 48, 12, 10.3109/10715762.2013.830718 Sandström, 2006, Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle, J. Physiol., 575, 251, 10.1113/jphysiol.2006.110601 Scheele, 2009, ROS and myokines promote muscle adaptation to exercise, Trends Endocrinol. Metab., 20, 95, 10.1016/j.tem.2008.12.002 Schieven, 2002, Hypochlorous acid activates tyrosine phosphorylation signal pathways leading to calcium signaling and TNFalpha production, Antioxid. Redox Signal., 4, 501, 10.1089/15230860260196308 Shen, 2012, Analytical measurement of discrete hydrogen sulfide pools in biological specimens, Free Radic. Biol. Med., 52, 2276, 10.1016/j.freeradbiomed.2012.04.007 Sheu, 2006, Targeting antioxidants to mitochondria: a new therapeutic direction, Biochim. Biophys. Acta, 1762, 256, 10.1016/j.bbadis.2005.10.007 Smith, 2011, Mitochondria-targeted small molecule therapeutics and probes, Antioxid. Redox Signal., 15, 3021, 10.1089/ars.2011.3969 Smith, 2010, Animal and human studies with the mitochondria-targeted antioxidant MitoQ, Ann. N. Y. Acad. Sci., 1201, 96, 10.1111/j.1749-6632.2010.05627.x Smock, 2009, Sending signals dynamically, Science, 324, 198, 10.1126/science.1169377 Sobotta, 2015, Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling, Nat. Chem. Biol., 11, 64, 10.1038/nchembio.1695 Stadtman, 2005, Methionine oxidation and aging, Biochim. Biophys. Acta, 1703, 135, 10.1016/j.bbapap.2004.08.010 Stadtman, 2003, Free radical-mediated oxidation of free amino acids and amino acid residues in proteins, Amino Acids, 25, 207, 10.1007/s00726-003-0011-2 Stamler, 2001, Nitrosylation. The prototypic redox-based signaling mechanism, Cell, 106, 675, 10.1016/S0092-8674(01)00495-0 Stein, 2013, Redox biology of hydrogen sulfide: implications for physiology, pathophysiology, and pharmacology, Redox Biol., 1, 32, 10.1016/j.redox.2012.11.006 Strobel, 2011, Antioxidant supplementation reduces skeletal muscle mitochondrial biogenesis, Med. Sci. Sports Exerc., 43, 1017, 10.1249/MSS.0b013e318203afa3 Sun, 2010, Protein S-nitrosylation and cardioprotection, Circ. Res., 106, 285, 10.1161/CIRCRESAHA.109.209452 Szewczyk, 2002, Mitochondria as a pharmacological target, Pharmacol. Rev., 54, 101, 10.1124/pr.54.1.101 Szeto, 2014, First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics, Br. J. Pharmacol., 171, 2029, 10.1111/bph.12461 Szeto, 2011, Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development, Pharm. Res., 28, 2669, 10.1007/s11095-011-0476-8 Takano, 2005, Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase, Life Sci., 76, 1835, 10.1016/j.lfs.2004.10.031 ten Freyhaus, 2006, Novel Nox inhibitor VAS2870 attenuates PDGF-dependent smooth muscle cell chemotaxis, but not proliferation, Cardiovasc. Res., 71, 331, 10.1016/j.cardiores.2006.01.022 Theodorou, 2014, Passive smoking reduces and vitamin C increases exercise-induced oxidative stress: does this make passive smoking an anti-oxidant and vitamin C a pro-oxidant stimulus?, Biochem. Biophys. Res. Commun., 454, 131, 10.1016/j.bbrc.2014.10.042 Thomas, 2015, Signaling and stress: the redox landscape in NOS2 biology, Free Radic. Biol. Med., 87, 204, 10.1016/j.freeradbiomed.2015.06.002 Thomas, 2008, The chemical biology of nitric oxide: implications in cellular signaling, Free Radic. Biol. Med., 45, 18, 10.1016/j.freeradbiomed.2008.03.020 Tomanek, 2015, Proteomic responses to environmentally induced oxidative stress, J. Exp. Biol., 218, 1867, 10.1242/jeb.116475 Toyoda, 2004, Possible involvement of the alpha1 isoform of 5'AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 287, E166, 10.1152/ajpendo.00487.2003 Tsikas, 2012, Potential problems and pitfalls with the use of S-nitrosoglutathione and other S-nitrosothiols in physiology-oriented basic science, J. Physiol., 590, 6247, 10.1113/jphysiol.2012.237412 Tsikas, 2008, A critical review and discussion of analytical methods in the l-arginine/nitric oxide area of basic and clinical research, Anal. Biochem., 379, 139, 10.1016/j.ab.2008.04.018 Ushio-Fukai, 2009, Compartmentalization of redox signaling through NADPH oxidase-derived ROS, Antioxid. Redox Signal., 11, 1289, 10.1089/ars.2008.2333 Ushio-Fukai, 2006, Redox signaling in angiogenesis: role of NADPH oxidase, Cardiovasc. Res., 71, 226, 10.1016/j.cardiores.2006.04.015 Venditti, 2014, Vitamin E supplementation modifies adaptive responses to training in rat skeletal muscle, Free Radic. Res., 48, 1179, 10.3109/10715762.2014.937341 Veskoukis, 2008, Effects of xanthine oxidase inhibition on oxidative stress and swimming performance in rats, Appl. Physiol. Nutr. Metab., 33, 1140, 10.1139/H08-102 Viña, 2013, The free radical theory of aging revisited: the cell signaling disruption theory of aging, Antioxid. Redox Signal., 19, 779, 10.1089/ars.2012.5111 Vogt, 1995, Oxidation of methionyl residues in proteins: tools, targets, and reversal, Free Radic. Biol. Med., 18, 93, 10.1016/0891-5849(94)00158-G Wadley, 2015, Monitoring changes in thioredoxin and over-oxidised peroxiredoxin in response to exercise in humans, Free Radic. Res., 49, 290, 10.3109/10715762.2014.1000890 Weissig, 2003, Mitochondrial-targeted drug and DNA delivery, Crit. Rev. Ther. Drug Carrier Syst., 20, 1, 10.1615/CritRevTherDrugCarrierSyst.v20.i1.10 Winterbourn, 2015, Are free radicals involved in thiol-based redox signaling?, Free Radic. Biol. Med., 80, 164, 10.1016/j.freeradbiomed.2014.08.017 Winterbourn, 2014, The challenges of using fluorescent probes to detect and quantify specific reactive oxygen species in living cells, Biochim. Biophys. Acta, 1840, 730, 10.1016/j.bbagen.2013.05.004 Winterbourn, 2013, The biological chemistry of hydrogen peroxide, Methods Enzymol., 528, 3, 10.1016/B978-0-12-405881-1.00001-X Winterbourn, 2008, Reconciling the chemistry and biology of reactive oxygen species, Nat. Chem. Biol., 4, 278, 10.1038/nchembio.85 Winterbourn, 2008, Thiol chemistry and specificity in redox signaling, Free Radic. Biol. Med., 45, 549, 10.1016/j.freeradbiomed.2008.05.004 Wood, 2003, Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling, Science, 300, 650, 10.1126/science.1080405 Xia, 2003, Skeletal muscle sarcoplasmic reticulum contains a NADH-dependent oxidase that generates superoxide, Am. J. Physiol. Cell Physiol., 285, C215, 10.1152/ajpcell.00034.2002 Xie, 2006, Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells, J. Biol. Chem., 281, 6366, 10.1074/jbc.M511178200 Yang, 2002, Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid, J. Biol. Chem., 277, 38029, 10.1074/jbc.M206626200 Zhang, 2012, Sub-cellular targeting of constitutive NOS in health and disease, J. Mol. Cell. Cardiol., 52, 341, 10.1016/j.yjmcc.2011.09.006 Zhang, 2008, Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide, Circ. Res., 102, 328, 10.1161/CIRCRESAHA.107.163253 Zhao, 2004, Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury, J. Biol. Chem., 279, 34682, 10.1074/jbc.M402999200 Zmijewski, 2010, Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase, J. Biol. Chem., 285, 33154, 10.1074/jbc.M110.143685