title: Activation of Akt by SC79 protects myocardiocytes from oxygen and glucose deprivation (OGD)/re-oxygenation.
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.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Koulong
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Hui-He
authors.initials: HH
authors.lastname: Lu
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: C000614067:AKT activator SC79; D000085:Acetates; D001578:Benzopyrans; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D010100:Oxygen
keywords: Akt; SC79; ischemic heart diseases; myocardial cells; oxygen glucose deprivation (OGD)