GLP-1(9-36), a GLP-1 cleavage product, protects against oxidative stress and apoptosis through PI3K/Akt/NOS pathway in H9c2 cardiomyoblasts
Abstract GLP-1(7–36), a major active form of GLP-1 hormone, is rapidly cleaved by dipeptidyl peptidase-4 to generate a truncated metabolite, GLP-1(9–36) which has a low affinity for GLP-1 receptor (GLP-1R). GLP-1(7–36) has been shown to have protective effects on cardiovascular system through GLP-1R-dependent way. Nevertheless, the cardioprotective effects of GLP-1(9–36) have not fully understood. The present study investigated the effects of GLP-1(9–36), including its underlying mechanisms against oxidative stress and apoptosis in H9c2 cardiomyoblasts. Here, we reported that GLP-1(9–36) protects H9c2 cardiomyoblasts from hydrogen peroxide (H2O2)-induced oxidative stress by promoting the synthesis of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1. In addition, treatment with GLP-1(9–36) suppressed H2O2-induced apoptosis by attenuating caspase-3 activity and upregulating proapoptotic proteins, Bcl-2 and Bcl-xL. These protective effects of GLP-1(9–36) are attenuated by blockade of PI3K-mediated Akt phosphorylation and prevention of nitric oxide synthase (NOS)-induced NO production. Collectively, GLP-1(9–36) represents the potential therapeutic target for prevention of oxidative stress and apoptosis in the heart.