A novel peptide HSP-17 ameliorates oxidative stress injury and apoptosis in H9c2 cardiomyocytes by activating the PI3K/Akt pathway.

Abstract

Oxidative stress and cell apoptosis play pivotal roles in the pathogenesis of doxorubicin (DOX)-induced myocardial injury. Heat shock protein-derived peptide (HSP-17) is a peptide which is low-expressed in DOX treated mouse heart tissue. It has high bioactivity and interspecies sequence consistency, and is predicted to have myocardial protective effect. Firstly, we added 1 µM DOX to H9c2 cell culture medium for 24 hours to construct the myocardial cytotoxicity model. Then we detected the effect of HSP-17 on DOX induced H9c2 cardiomyocyte injury by measuring cell viability and lactate dehydrogenase (LDH) level. In addition, reactive oxygen species (ROS) and tetraethylbenzimidazolylcarbocyanine iodide kits are used to evaluate the effect of the HSP-17 peptide on DOX-induced oxidative stress injury to cardiomyocytes, and the detection of apoptosis related proteins and flow cytometry were applied to detect the level of apoptosis. Furthermore, the protein expression levels [phosphorylated Akt (p-Akt) and phosphorylated PI3K (p-PI3K)] of the PI3K/Akt pathway were also detected by western blotting. We found that the HSP-17 peptide can increase cell viability, protect mitochondrial potential, reduce LDH levels, and reduce ROS and cardiomyocyte apoptosis. In addition, we also observed that HSP-17 upregulated the expression level of p-Akt, and LY294002, a typical inhibitor of PI3K/Akt, was found to eliminate the protective roles of HSP-17. In conclusion, this study demonstrated that the HSP-17 peptide protected H9c2 cells against oxidative stress and apoptosis via PI3K/Akt pathway activation, which provides a new idea for the treatment of DOX-induced myocardial injury.