Involvement of DJ-1 in ischemic preconditioning-induced delayed cardioprotection in vivo

Abstract

DJ‑1 protein, as a multifunctional intracellular protein, has been demonstrated to serve a critical role in regulating cell survival and oxidative stress. To provide invivo evidence that DJ‑1 is involved in the delayed cardioprotection induced by ischemic preconditioning (IPC) against oxidative stress caused by ischemia/reperfusion (I/R), the present study subjected male Sprague‑Dawley rats to IPC (3cycles of 5‑min coronary occlusion/5‑min reperfusion) 24h prior to I/R (30‑min coronary occlusion/120‑min reperfusion). A lentiviral vector containing short hairpin RNA was injected into the left ventricle three weeks prior to IPC, to knockdown DJ‑1 insitu. Lactate dehydrogenase (LDH) and creatine kinase‑MB (CK‑MB) release, infarct size, cardiac function, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, malondialdehyde (MDA), intracellular reactive oxygen species (ROS), and DJ‑1 protein expression levels were assessed. IPC caused a significant increase in the expression levels of DJ‑1 protein. In addition, IPC reduced LDH and CK‑MB release, attenuated myocardial infarct size, improved cardiac function following I/R, and inhibited the elevation of ROS and MDA and the decrease in activities of the antioxidant enzymes SOD, CAT and GPx. However, insitu knockdown of DJ‑1 attenuated the IPC‑induced delayed cardioprotection, and reversed the inhibitory effect of IPC on I/R‑induced oxidative stress. The present study therefore provided novel evidence that DJ‑1 is involved in the delayed cardioprotection of IPC against I/R injury invivo. Notably, DJ‑1 is required for IPC to inhibit I/R‑induced oxidative stress.