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Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3beta signaling pathway
Experimental & Molecular Medicine ; : 53-61, 2011.
Artículo en Inglés | WPRIM | ID: wpr-48414
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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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Transducción de Señal / Línea Celular / Morfolinas / Western Blotting / Cromonas / Especies Reactivas de Oxígeno / Apoptosis / Estrés Oxidativo / Fosfatidilinositol 3-Quinasas / Reacción en Cadena de la Polimerasa de Transcriptasa Inversa Límite: Animales / Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2011 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Transducción de Señal / Línea Celular / Morfolinas / Western Blotting / Cromonas / Especies Reactivas de Oxígeno / Apoptosis / Estrés Oxidativo / Fosfatidilinositol 3-Quinasas / Reacción en Cadena de la Polimerasa de Transcriptasa Inversa Límite: Animales / Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2011 Tipo del documento: Artículo