REDD1 knockdown protects H9c2 cells against myocardial ischemia/reperfusion injury through Akt/mTORC1/Nrf2 pathway-ameliorated oxidative stress: An in vitro study.

Oxidative stress plays a significant role involved in myocardial ischemia/reperfusion (MI/R) injury. The regulated in development and DNA damage response 1 (REDD1) is an mTORC1 inhibitor participating in response to hypoxia and oxidative stress. However, whether and how REDD1 is associated with MI/R injury are unclear. By investigating an in vitro model, we reveal that REDD1 is induced by HIF-1α in H9c2 cells subjected to oxygen/glucose deprivation followed by reperfusion (OGD/R). Further, cells depleted of REDD1 exhibit less OGD/R-induced injury, as evidenced by reduced lactate dehydrogenase (LDH) release and decreased apoptosis. Moreover, Nrf2 silencing abrogates REDD1 depletion-reduced reactive oxygen species (ROS) level and OGD/R-induced injury, indicating that the REDD1 depletion-mediated cellular protection is dependent on Nrf2-eliminated oxidative stress. Lastly, REDD1 depletion activates Akt/mTORC1 pathway following OGD/R treatment, and inhibition of this pathway using both LY294002 and rapamycin abrogates REDD1 effects. Altogether, these results suggest that REDD1 depletion protects H9c2 cells against OGD/R-induced injury through ameliorating oxidative stress, which is modulated by Akt/mTORC1/Nrf2 signaling. Our study may also reveal REDD1 as a potential therapeutic target for improving cardioprotection in MI/R injury treatment.