Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mangmool, S; Hemplueksa, P; Parichatikanond, W; Chattipakorn, N.
Epac is required for GLP-1R-mediated inhibition of oxidative stress and apoptosis in cardiomyocytes.
Mol Endocrinol. 2015; 29(4): 583-596.
Doi: 10.1210/me.2014-1346
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- Co-Autor*innen der Med Uni Graz
- Parichatikanond Warisara
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- Abstract:
- 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 β-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 H2O2-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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis - drug effects
- Caspase 3 - metabolism
- Cell Survival - drug effects
- Glucagon-Like Peptide-1 Receptor - metabolism
- Guanine Nucleotide Exchange Factors - genetics Guanine Nucleotide Exchange Factors - metabolism
- Hydrogen Peroxide - pharmacology
- Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism
- Oxidative Stress - drug effects
- Peptides - pharmacology
- Proto-Oncogene Proteins c-bcl-2 - metabolism
- RNA, Small Interfering -
- Rats -
- Reactive Oxygen Species - metabolism
- Venoms - pharmacology