Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3 beta signaling pathway
- Authors
- Jun, Hyoung-Oh; Kim, Dong-hun; Lee, Sae-Won; Lee, Hye Shin; Seo, Ji Hae; Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk; Min, Bon Hong; Kim, Kyu-Won
- Issue Date
- 31-1월-2011
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- apoptosis; clusterin; glycogen synthase kinase 3 beta; myocytes, cardiac; oxidative stress; proto-oncogene proteins c-akt
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.43, no.1, pp.53 - 61
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 43
- Number
- 1
- Start Page
- 53
- End Page
- 61
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/113242
- DOI
- 10.3858/emm.2011.43.1.006
- ISSN
- 1226-3613
- 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-3 beta. 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-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.
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