Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3beta signaling pathway.
10.3858/emm.2011.43.1.006
- Author:
Hyoung Oh JUN
1
;
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
Author Information
1. NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea. qwonkim@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
clusterin;
glycogen synthase kinase 3beta;
myocytes, cardiac;
oxidative stress;
proto-oncogene proteins c-akt
- MeSH:
Animals;
*Apoptosis;
Blotting, Western;
Caspase 3/metabolism;
Caspase 9/metabolism;
Cell Line;
Chromones/pharmacology;
Clusterin/metabolism/*pharmacology;
Glycogen Synthase Kinase 3/metabolism;
Humans;
Hydrogen Peroxide/pharmacology;
LDL-Receptor Related Protein 2/metabolism;
Morpholines/pharmacology;
Myocytes, Cardiac/*metabolism;
*Oxidative Stress;
Phosphatidylinositol 3-Kinases/metabolism;
Proto-Oncogene Proteins c-akt/metabolism;
RNA, Small Interfering;
Rats;
Reactive Oxygen Species/pharmacology;
Reverse Transcriptase Polymerase Chain Reaction;
*Signal Transduction/drug effects
- From:Experimental & Molecular Medicine
2011;43(1):53-61
- CountryRepublic of Korea
- Language:English
-
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.
