Epac is required for GLP-1R-mediated inhibition of oxidative stress and apoptosis in cardiomyocytes

• Main Authors: Mangmool S., Hemplueksa P., Parichatikanond W., Chattipakorn N.
• Format: Article
• Published: The Endocrine Society 2015
• Subjects: Molecular Biology; Endocrinology
• Online Access: http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84926335902&origin=inward; http://cmuir.cmu.ac.th/handle/6653943832/38447
• Institution: Chiang Mai University

© 2015 by the Endocrine Society. Although the cardioprotective effects of glucagon-like peptide-1 and its analogs have been reported, the exact mechanisms of the glucagon-like peptide-1 receptor (GLP-1R) signaling pathway in the heart are still unclear. Activation of the GLP-1R has been shown to increase cAMP levels, thus eliciting protein kinase A- and exchange protein activated by cAMP (Epac)-dependent signaling pathways in pancreatic b-cells. However, which pathway plays an important role in the antioxidant and antiapoptotic effects of GLP-1R activation in the heart is not known. In this study, we demonstrated that stimulation of GLP-1Rs with exendin-4 attenuated H<inf>2</inf>O<inf>2</inf>-induced reactive oxygen species production and increased the synthesis of antioxidant enzymes, catalase, glutathione peroxidase-1, and manganese superoxide dismutase that is dependent on Epac. Additionally, exendin-4 has an antiapoptotic effect by decreasing a number of apoptotic cells, inhibiting caspase-3 activity, and enhancing the expression of antiapoptotic protein B-cell lymphoma 2, which is mediated through both protein kinase A- and Epac-dependent pathways. These data indicate a critical role for Epac in GLP-1R-mediated cardioprotection.