Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3beta signaling pathway
Experimental & Molecular Medicine
; : 53-61, 2011.
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| ID: wpr-48414
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WPRO
ABSTRACT
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-3beta. 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-3beta. 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-3beta phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-3beta signaling mediates anti-apoptotic effect of clusterin.
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Asunto principal:
Transducción de Señal
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Línea Celular
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Morfolinas
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Western Blotting
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Cromonas
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Especies Reactivas de Oxígeno
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Apoptosis
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Estrés Oxidativo
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Fosfatidilinositol 3-Quinasas
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Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
Límite:
Animals
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Humans
Idioma:
En
Revista:
Experimental & Molecular Medicine
Año:
2011
Tipo del documento:
Article