Peripheral Administration of Human Adrenomedullin and Its Binding Protein Attenuates Stroke-Induced Apoptosis and Brain Injury in Rats
Tóm tắt
Stroke is a leading cause of death and the primary medical cause of acquired adult disability worldwide. The progressive brain injury after acute stroke is partly mediated by ischemia-elicited inflammatory responses. The vasoactive hormone adrenomedullin (AM), upregulated under various inflammatory conditions, counterbalances inflammatory responses. However, regulation of AM activity in ischemic stroke remains largely unknown. Recent studies have demonstrated the presence of a specific AM binding protein (that is, AMBP-1) in mammalian blood. AMBP-1 potentiates AM biological activities. Using a rat model of focal cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO), we found that plasma levels of AM increased significantly, whereas plasma levels of AMBP-1 decreased significantly after stroke. When given peripherally early after MCAO, exogenous human AM in combination with human AMBP-1 reduced brain infarct volume 24 and 72 h after MCAO, an effect not observed after the treatment by human AM or human AMBP-1 alone. Furthermore, treatment of human AM/AMBP-1 reduced neuron apoptosis and morphological damage, inhibited neutrophil infiltration in the brain and decreased serum levels of S100B and lactate. Thus, human AM/AMBP-1 has the ability to reduce stroke-induced brain injury in rats. AM/AMBP-1 can be developed as a novel therapeutic agent for patients with ischemic stroke.
Tài liệu tham khảo
Thom T, et al. (2006) Heart disease and stroke statistics: 2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 113:e85–151.
Broderick JP. (2004) William M. Feinberg Lecture: stroke therapy in the year 2025: burden, breakthroughs, and barriers to progress. Stroke. 35:205–11.
Goldstein LB. (2007) Acute ischemic stroke treatment in 2007. Circulation. 116:1504–14.
Chacon MR, Jensen MB, Sattin JA, Zivin JA. (2008) Neuroprotection in cerebral ischemia: emphasis on the SAINT trial. Curr. Cardiol. Rep. 10:37–42.
Switzer JA, Hess DC. (2008) Development of regional programs to speed treatment of stroke. Curr. Neurol. Neurosci. Rep. 8:35–42.
Kitamura K, et al. (1993) Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun. 192:553–60.
Isumi Y, Kubo A, Katafuchi T, Kangawa K, Minamino N. (1999) Adrenomedullin suppresses interleukin-1α-induced tumor necrosis factor-β production in Swiss 3T3 cells. FEBS Lett. 463:110–14.
Kubo A, et al. (1998) Production of adrenomedullin in macrophage cell line and peritoneal macrophage. J Biol. Chem. 273:16730–16738.
Iwamoto M, et al. (2003) Adrenomedullin inhibits pressure-induced mesangial MCP-1 expression through activation of protein kinase A. J. Nephrol. 16:673–81.
Gonzalez-Rey E, Chorny A, Varela N, Robledo G, Delgado M. (2006) Urocortin and adrenomedullin prevent lethal endotoxemia by down-regulating the inflammatory response. Am. J. Pathol. 168:1921–30.
Elsasser TH, et al. (1999) Adrenomedullin binding protein in the plasma of multiple species: characterization by radioligand blotting. Endocrinology. 140:4908–11.
Pio R, et al. (2001) Complement factor H is a serum binding protein for adrenomedullin: the resulting complex modulates the bioactivities of both partners. J. Biol. Chem. 276:12292–300.
Zhou M, Ba ZF, Chaudry IH, Wang P. (2002) Adrenomedullin binding protein-1 modulates vascular responsiveness to adrenomedullin in late sepsis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283:R553–60.
Wu R, Zhou M, Wang P. (2003) Adrenomedullin and adrenomedullin binding protein-1 downregulate TNF-alpha in macrophage cell line and rat Kupffer cells. Regul. Pept. 112:19–26.
Xia CF, Yin H, Borlongan CV, Chao J, Chao L. (2004) Adrenomedullin gene delivery protects against cerebral ischemic injury by promoting astrocyte migration and survival. Hum. Gene Ther. 15:1243–54.
Miyashita K, et al. (2006) The neuroprotective and vasculo-neuro-regenerative roles of adreno-medullin in ischemic brain and its therapeutic potential. Endocrinology. 147:1642–53.
Tixier E, et al. (2008) Adrenomedullin protects neurons against oxygen glucose deprivation stress in an autocrine and paracrine manner. J. Neurochem. 106:1388–403.
Hanabusa K, et al. (2005) Adrenomedullin enhances therapeutic potency of mesenchymal stem cells after experimental stroke in rats. Stroke. 36:853–8.
Yang S, Zhou M, Chaudry IH, Wang P. (2002) Novel approach to prevent the transition from the hyperdynamic phase to the hypodynamic phase of sepsis: role of adrenomedullin and adrenomedullin binding protein-1. Ann. Surg. 236:625–33.
Carrizo GJ, et al. (2007) Adrenomedullin and adrenomedullin-binding protein-1 downregulate inflammatory cytokines and attenuate tissue injury after gut ischemia-reperfusion. Surgery. 141:245–53.
Wu R, et al. (2005) Mechanisms responsible for vascular hyporesponsiveness to adrenomedullin after hemorrhage: the central role of adrenomedullin binding protein-1. Ann. Surg. 242:115–23.
Wang SM, Yang WL. (2009) Circulating hormone adrenomedullin and its binding protein protect neural cells from hypoxia-induced apoptosis. Biochim. Biophys. Acta. 1790:361–7.
Wang H, et al. (2010) Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats. J. Cereb. Blood Flow Metab. 30:493–504.
Dwivedi AJ, et al. (2007) Adrenomedullin and adrenomedullin binding protein-1 prevent acute lung injury after gut ischemia-reperfusion. J. Am. Coll. Surg. 205:284–93.
Yang J, et al. (2009) Human adrenomedullin and its binding protein attenuate organ injury and reduce mortality after hepatic ischemia-reperfusion. Ann. Surg. 249:310–7.
Qiang X, Wu R, Ji Y, Zhou M, Wang P. (2008) Purification and characterization of human adrenomedullin binding protein-1. Mol. Med. 14:443–50.
Cui X, et al. (2005) Adrenomedullin and its binding protein attenuate the proinflammatory response after hemorrhage. Crit. Care Med. 33:391–8.
Zhou M, Simms HH, Wang P. (2004) Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis. Ann. Surg. 240:321–30.
Wu R, et al. (2008) Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion. PLoS. ONE. 3:e2026.
Lynch JR, et al. (2004) Novel diagnostic test for acute stroke. Stroke 35:57–63.
Dogan A, et al. (1997) Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. J. Cereb. Blood Flow Metab. 17:19–25.
Hosomi N, et al. (2004) Plasma adrenomedullin and carotid atherosclerosis in atherothrombotic ischemic stroke. J. Hypertens. 22:1945–51.
Shimosawa T, Fujita T. (2005) Adrenomedullin and its related peptide. Endocr. J. 52:1–10.
Martinez A, et al. (2004) Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator. Biochem. J. 383:413–8.
Naked GM, et al. (2000) Deficiency of human complement factor I associated with lowered factor H. Clin. Immunol. 96:162–7.
Menzies SA, Betz AL, Hoff JT. (1993) Contributions of ions and albumin to the formation and resolution of ischemic brain edema. J. Neurosurg. 78:257–66.
Pan W, Kastin AJ. (2007) Tumor necrosis factor and stroke: role of the blood-brain barrier. Prog. Neurobiol. 83:363–74.
Muir KW, Tyrrell P, Sattar N, Warburton E. (2007) Inflammation and ischaemic stroke. Curr. Opin. Neurol. 20:334–42.
Liu T, et al. (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke. 25:1481–8.
Liu T, et al. (1993) Interleukin-1 beta mRNA expression in ischemic rat cortex. Stroke. 24:1746–50.
Wang X, Yue TL, Young PR, Barone FC, Feuerstein GZ. (1995) Expression of interleukin-6, c-fos, and zif268 mRNAs in rat ischemic cortex. J. Cereb. Blood Flow Metab. 15:166–71.
Emsley HC, et al. (2007) Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurol. 7:5.
Jacob A, et al. (2007) Pro-inflammatory cytokines from Kupffer cells downregulate hepatocyte expression of adrenomedullin binding protein-1. Biochim. Biophys. Acta. 1772:766–72.
Graham SH, Chen J. (2001) Programmed cell death in cerebral ischemia. J. Cereb. Blood Flow Metab. 21:99–109.
Northington FJ, Ferriero DM, Flock DL, Martin LJ. (2001) Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis. J. Neurosci. 21:1931–8.
Kato H, Kogure K. (1999) Biochemical and molecular characteristics of the brain with developing cerebral infarction. Cell Mol. Neurobiol. 19:93–108.
Newcomb JD, et al. (2006) Timing of cord blood treatment after experimental stroke determines therapeutic efficacy. Cell Transplant. 15:213–23.
Ferrer I. (2006) Apoptosis: future targets for neuroprotective strategies. Cerebrovasc. Dis. 21 Suppl 2:9–20.
Jordan J, Ikuta I, Garcia-Garcia J, Calleja S, Segura T. (2007) Stroke pathophysiology: management challenges and new treatment advances. J. Physiol. Biochem. 63:261–77.
Matsuo Y, et al. (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat: effects of neutrophil depletion. Stroke. 25:1469–75.
Chen H, et al. (1994) Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat. Ann. Neurol. 35:458–63.
Saito Y, Nakagawa C, Uchida H, Sasaki F, Sakakibara H. (2001) Adrenomedullin suppresses fMLP-induced upregulation of CD11b of human neutrophils. Inflammation. 25:197–201.
Sakata J, et al. (1993) Molecular cloning and biological activities of rat adrenomedullin, a hypotensive peptide. Biochem. Biophys. Res. Commun. 195:921–7.
Hurtado O, et al. (2010) Lack of adrenomedullin, but not complement factor H, results in larger infarct size and more extensive brain damage in a focal ischemia model. Neuroscience. 171:885–92.