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

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38 Citations (Scopus)

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 H 2O 2-induced apoptosis by triggering the activation of Akt and GSK-3β. Treatment with H 2O 2induces 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 H 2O 2, thereby recovers cell viability. The protective effect of clusterin on H 2O 2-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
Publication statusPublished - 2011 Jan 31

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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  • Cite this

    Jun, H. O., Kim, D. H., Lee, S. W., Lee, H. S., Seo, J. H., Kim, J. H., Kim, J. H., Yu, Y. S., Min, B. H., & Kim, K. W. (2011). Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3β signaling pathway. Experimental and Molecular Medicine, 43(1), 53-61. https://doi.org/10.3858/emm.2011.43.1.006