Metformin differentially activates ER stress signaling pathways without inducing apoptosis
2012 | journal article. A publication with affiliation to the University of Göttingen.
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- Authors
- Quentin, Thomas; Steinmetz, Michael ; Poppe, Andrea; Thoms, Sven
- Abstract
- Endoplasmic reticulum stress signaling (ERSS) plays an important role in the pathogenesis of diabetes and heart disease. The latter is a common comorbidity of diabetes and worsens patient outcome. Results from clinical studies suggest beneficial effects of metformin - a widely used oral drug for the treatment of type 2 diabetes - on the heart of diabetic patients with heart failure. We therefore analyzed the effect of metformin on ERSS in primary rat cardiomyocytes. We found that metformin activates the PERK-ATF4 but not the ATF6 or IRE1-XBP1 branch in ERSS and leads to a strong upregulation of CHOP mRNA and protein. Surprisingly, long-term induction of CHOP by metformin is not accompanied by apoptosis even though CHOP is regarded to be a mediator of ER-stress-induced apoptosis. In conclusion, metformin induces distinct ER stress pathways in cardiomyocytes and our results indicate that CHOP is not necessarily a mediator of apoptosis. Metformin might exert its cardioprotective effect through selective activation of ERSS pathways in the cardiomyocyte.
- Issue Date
- 2012
- Journal
- Disease Models & Mechanisms
- ISSN
- 1754-8403
- Language
- English