Exendin-4 Protects Against Myocardial Ischemia-Reperfusion Injury by Upregulation of SIRT1 and SIRT3 and Activation of AMPK

In conclusion, Exendin-4 cardioprotective effect against I/R involves activa tion of SIRT1 and SIRT3.Graphical AbstractExendin-4 could scavenge free radical directly, upregulate p53, and  through upregulation of SIRT1 and stimulating SIRT1 nuclear accumulation. In addition, Exendin-4 also upregulates SIRT3 which plays an essential role in the upregulation of antioxidants, inhibition of reactive oxygen species (ROS) generation, and prevention of mitochondria damage. Accordingly, SI RT1 induces the deacetylation of PGC-1α and p53 and is able to bind p-FOXO-1. This results in inhibition of cardiomyocyte apoptosis through increasing Bcl-2 levels, activity, and levels of MnSOD; decreasing expression of Bax; decreasing cytochrome C release; and improving mitochondria biogenesis th rough upregulation of Mfn-2.
Source: Journal of Cardiovascular Translational Research - Category: Cardiology Source Type: research