Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3β signaling pathway

被引：0

作者：

Hyoung-Oh Jun

Dong-hun Kim

Sae-Won Lee

Hye Shin Lee

Ji Hae Seo

Jeong Hun Kim

Jin Hyoung Kim

Young Suk Yu

Bon Hong Min

Kyu-Won Kim

机构：

[1] NeuroVascular Coordination Research Center,Department of Radiology

[2] College of Pharmacy and Research Institute of Pharmaceutical Sciences,Department of Ophthalmology

[3] Seoul National University,Department of Pharmacology and BK21 Program for Medical Sciences

[4] Seoul 151-742,Department of Molecular Medicine and Biopharmaceutical Sciences

[5] Korea.,undefined

[6] College of Medicine,undefined

[7] Sooncheonhyang University,undefined

[8] Bucheon 420-767,undefined

[9] korea.,undefined

[10] Clinical Research Institute,undefined

[11] Seoul National University Hospital,undefined

[12] Seoul 110-744,undefined

[13] Korea.,undefined

[14] College of Medicine,undefined

[15] Seoul National University and Seoul Artificial Eye Center Clinical Research Institute,undefined

[16] Seoul National University Hospital,undefined

[17] Seoul 110-744,undefined

[18] Korea.,undefined

[19] College of Medicine,undefined

[20] Korea University,undefined

[21] Seoul 136-701,undefined

[22] Korea.,undefined

[23] Graduate School of Convergence Science and Technology,undefined

[24] Seoul National University,undefined

[25] Seoul 151-742,undefined

[26] Korea.,undefined

来源：

Experimental & Molecular Medicine | 2011年 / 43卷

关键词：

apoptosis; clusterin; glycogen synthase kinase 3β; myocytes, cardiac; oxidative stress; proto-oncogene proteins c-akt;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Clusterin is a secretory glycoprotein, which is highly up-regulated in a variety of normal and injury tissues undergoing apoptosis including infarct region of the myocardium. Here, we report that clusterin protects H9c2 cardiomyocytes from H2O2-induced apoptosis by triggering the activation of Akt and GSK-3β. Treatment with H2O2 induces apoptosis of H9c2 cells by promoting caspase cleavage and cytochrome c release from mitochondria. However, co-treatment with clusterin reverses the induction of apoptotic signaling by H2O2, thereby recovers cell viability. The protective effect of clusterin on H2O2-induced apoptosis is impaired by PI3K inhibitor LY294002, which effectively suppresses clusterin-induced activation of Akt and GSK-3β. In addition, the protective effect of clusterin is independednt on its receptor megalin, because inhibition of megalin has no effect on clusturin-mediated Akt/GSK-3β phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-3β signaling mediates anti-apoptotic effect of clusterin.

引用

页码：53 / 61

页数：8

共 228 条

[1]

Ammar H(2008)Clusterin activates survival through the phosphatidylinositol 3-kinase/Akt pathway J Biol Chem 283 12851-12861

[2]

Closset JL(1983)Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid J Biol Chem 258 7714-7720

[3]

Blaschuk O(2002)Clusterin protects renal tubular epithelial cells from gentamicin-mediated cytotoxicity Am J Physiol Renal Physiol 282 F703-F709

[4]

Burdzy K(2004)Opioid-induced cardioprotection occurs Circ Res 94 960-966

[5]

Fritz IB(1998) glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts Arterioscler Thromb Vasc Biol 18 665-672

[6]

Girton RA(2002)Distribution and synthesis of apolipoprotein J in the atherosclerotic aorta Int J Biochem Cell Biol 34 427-431

[7]

Sundin DP(2009)Clusterin Circ Res 104 1240-1252

[8]

Rosenberg ME(2007)Role of glycogen synthase kinase-3beta in cardioprotection Curr Eye Res 32 693-698

[9]

Gross ER(2010)The role of clusterin in Invest Ophthalmol Vis Sci 51 561-566

[10]

Hsu AK(1995) ischemia of human retinal endothelial cells J Biol Chem 270 13070-13075

← 1 2 3 4 5 6 7 8 9 10 →