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KMID : 0620920110430010053
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Experimental & Molecular Medicine
2011 Volume.43 No. 1 p.53 ~ p.61
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Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3β signaling pathway
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Jun Hyoung-Oh
Kim Dong-Hun
Lee Sae-Won
Lee Hye-Shin
Seo Ji-Hae
Kim Jeong-Hun
Kim Jin-Hyoung
Yu Young-Suk
Min Bon-Hong
Kim Kyu-Won
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Abstract
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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.
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KEYWORD
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apoptosis, clusterin, glycogen synthase kinase 3β, myocytes, cardiac, oxidative stress, proto-oncogene proteins c-akt
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