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

Koulong Zheng; Qing Zhang; Gang Lin; Yefei Li; Zhenqiang Sheng; Jue Wang; Liang Chen; Hui-he Lu

doi:10.18632/oncotarget.14785

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Research Papers:

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

Koulong Zheng, Qing Zhang, Gang Lin, Yefei Li, Zhenqiang Sheng, Jue Wang, Liang Chen and Hui-he Lu _

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Oncotarget. 2017; 8:14978-14987. https://doi.org/10.18632/oncotarget.14785

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Abstract

Koulong Zheng1, Qing Zhang1, Gang Lin1, Yefei Li1, Zhenqiang Sheng1, Jue Wang1, Liang Chen1, Hui-he Lu1

1Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China

Correspondence to:

Hui-he Lu, email: [email protected]

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.

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Research Papers:

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

Abstract