Exp Mol Med.
2011 Jan;43(1):53-61. 10.3858/emm.2011.43.1.006.
Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3beta signaling pathway
- Affiliations
-
- 1NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea. qwonkim@snu.ac.kr
- 2Department of Radiology, College of Medicine, Sooncheonhyang University, Bucheon 420-767, korea.
- 3Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
- 4Department of Ophthalmology, College of Medicine, Seoul National University and Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
- 5Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul 136-701, Korea.
- 6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea.
- KMID: 991623
- DOI: http://doi.org/10.3858/emm.2011.43.1.006
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.
Keyword
MeSH Terms
-
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
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Ferulic acid regulates the AKT/GSK-3beta/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- PS-341-Induced Apoptosis is Related to JNK-Dependent Caspase 3 Activation and It is Negatively Regulated by PI3K/Akt-Mediated Inactivation of Glycogen Synthase Kinase-3beta in Lung Cancer Cells
- Acetaminophen Induced Cytotoxicity and Altered Gene Expression in Cultured Cardiomyocytes of H9C2 Cells
- Insulin-like growth factor-1 improves diabetic cardiomyopathy through antioxidative and anti-inflammatory processes along with modulation of Akt/GSK-3β signaling in rats
- CTLA4-Ig protects tacrolimus-induced oxidative stress via inhibiting the AKT/FOXO3 signaling pathway in rats
