title: Salidroside inhibits oxygen glucose deprivation (OGD)/re-oxygenation-induced H9c2 cell necrosis through activating of Akt-Nrf2 signaling.
abstract: Oxygen glucose deprivation (OGD)/re-oxygenation has been applied to cultured cardiomyocytes to create a cellular model of ischemic heart damage. In the current study, we explored the potential role of salidroside against OGD/re-oxygenation-induced damage in H9c2 cardiomyocytes, and studied the underlying mechanisms. We found that OGD/re-oxygenation primarily induced necrosis in H9c2 cells, which was inhibited by salidroside. Salidroside suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D (Cyp-D) association as well as mitochondrial membrane potential (MMP) decrease in H9c2 cells. Meanwhile, salidroside activated Akt and promoted transcription of NF-E2-related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1)). Significantly, Nrf2 shRNA knockdown or Akt inhibitors (LY 294002 and wortmannin) not only prevented salidroside-induced HO-1/NQO-1 transcription, but also alleviated salidroside-mediated cytoprotective effect against OGD/re-oxygenation in H9c2 cells. These observations suggest that salidroside activates Nrf2-regulated anti-oxidant signaling, and protects against OGD/re-oxygenation-induced H9c2 cell necrosis via activation of Akt signaling.
authors: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Koulong
authors: K
authors: Zheng
authors: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Zhenqiang
authors: Z
authors: Sheng
authors: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Yefei
authors: Y
authors: Li
authors: Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: nantongluhuihe@163.com.
authors: Huihe
authors: H
authors: Lu
mesh_terms: D000818:Animals; D002867:Chromones / Q000494:pharmacology; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced; D010100:Oxygen / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002867:Chromones; D000081406:Peptidyl-Prolyl Isomerase F; D005960:Glucosides; D009025:Morpholines; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010636:Phenols; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D021983:Cyclophilins; D005947:Glucose; C009172:rhodioloside; D010100:Oxygen
keywords: Akt and cardiomyocyte necrosis; Nrf2; Oxygen glucose deprivation (OGD)/re-oxygenation; Salidroside