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

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

Research output: Contribution to journalArticle

38 Scopus citations

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-3β. Treatment with H2O2induces 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.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalExperimental and Molecular Medicine
Volume43
Issue number1
DOIs
StatePublished - 31 Jan 2011

Keywords

  • Apoptosis
  • Cardiac
  • Clusterin
  • Glycogen synthase kinase 3β
  • Myocytes
  • Oxidative stress
  • Proto-oncogene proteins c-akt

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