Activation of Akt by SC79 protects myocardiocytes from oxygen and glucose deprivation (OGD)/re-oxygenation

Abstract

// Koulong Zheng 1 , Qing Zhang 1 , Gang Lin 1 , Yefei Li 1 , Zhenqiang Sheng 1 , Jue Wang 1 , Liang Chen 1 , Hui-he Lu 1 1 Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China Correspondence to: Hui-he Lu, email: nantongluhuihe@163.com Keywords: ischemic heart diseases, oxygen glucose deprivation (OGD), myocardial cells, SC79, Akt Received: December 08, 2016      Accepted: January 11, 2017      Published: January 21, 2017 ABSTRACT SC79 is a novel Akt activator. The current study tested its potential effect against oxygen and glucose deprivation (OGD)/re-oxygenation-induced myocardial cell death. We showed that SC79 activated Akt and protected H9c2 myocardial cells and primary murine myocardiocytes from OGD/re-oxygenation. Reversely, Akt inhibitor MK-2206 or Akt1 shRNA knockdown almost completely abolished SC79-mediated myocardial cytoprotection. SC79 treatment in H9c2 cells inhibited OGD/re-oxygenation-induced programmed necrosis pathway, evidenced by mitochondrial depolarization and cyclophilin D-p53-ANT-1 (adenine nucleotide translocator 1) association. Further, SC79 activated Akt downstream NF-E2-related factor 2 (NRF2) signaling to suppress OGD/re-oxygenation-induced reactive oxygen species (ROS) production. Reversely, NRF2 shRNA knockdown in H9c2 cells largely attenuated SC79-induced ROS scavenging ability and cytoprotection against OGD/re-oxygenation. Together, we conclude that activation of Akt by SC79 protects myocardial cells from OGD/re-oxygenation.