Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis $via$ Akt/GSK-$3{\beta}$ signaling pathway

  • Jun, Hyoung-Oh (NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Dong-Hun (Department of Radiology, College of Medicine, Sooncheonhyang University) ;
  • Lee, Sae-Won (Clinical Research Institute, Seoul National University Hospital) ;
  • Lee, Hye-Shin (NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Seo, Ji-Hae (NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Jeong-Hun (Department of Ophthalmology, College of Medicine, Seoul National University and Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital) ;
  • Kim, Jin-Hyoung (Department of Ophthalmology, College of Medicine, Seoul National University and Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital) ;
  • Yu, Young-Suk (Department of Ophthalmology, College of Medicine, Seoul National University and Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital) ;
  • Min, Bon-Hong (Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University) ;
  • Kim, Kyu-Won (NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
  • Accepted : 2010.12.13
  • Published : 2011.01.31
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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-$3{\beta}$. Treatment with $H_2O_2$ 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 $H_2O_2$, 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-$3{\beta}$. 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-$3{\beta}$ phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-$3{\beta}$ signaling mediates anti-apoptotic effect of clusterin.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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