title: Hyperglycemia attenuates remifentanil postconditioning-induced cardioprotection against hypoxia/reoxygenation injury in H9c2 cardiomyoblasts.
abstract: Hyperglycemia is proposed to be an independent risk factor for cardiovascular morbidity and mortality. Preclinical studies suggest that diabetes mellitus exacerbates myocardial ischemia/reperfusion injury and attenuates the effects of cardioprotective strategies. The cardioprotective effects of postconditioning with the opioid analgesic remifentanil against ischemia/reperfusion injury under the hyperglycemic condition remain contradictory. Therefore, the aim of this study was to investigate the mechanisms by which hyperglycemia affects cardioprotection induced by remifentanil postconditioning.
  
  
  
  H9c2 cardiomyoblasts were cultured under the normoglycemic or hyperglycemic condition. Cells were exposed to hypoxia/reoxygenation (H/R) injury followed by hypoxia postconditioning (HPC group) or remifentanil postconditioning (RPC group). Cell viability, injury, and apoptosis were measured after each postconditioning treatment. Activation of endoplasmic reticulum stress (ERS) was analyzed by examining the protein levels of GRP78, CHOP, cleaved caspase-12 and cleaved caspase-3.
  
  
  
  RPC significantly increased cell viability and reduced apoptosis in normoglycemic cardiomyoblasts, but not in hyperglycemic cardiomyoblasts. HPC and RPC markedly decreased the upregulation of GRP78, CHOP, cleaved caspase 12, and cleaved caspase 3 in response to H/R injury under the normoglycemic condition. Hyperglycemia significantly increased these ERS-associated biomarkers and apoptosis, which could not be reduced by HPC or RPC.
  
  
  
  Remifentanil postconditioning protected cardiomyoblasts from H/R injury under normoglycemia, at least in part, through inhibiting ERS-induced apoptosis. Hyperglycemia attenuated the cardioprotection conferred by remifentanil postconditioning, likely as a result of the exacerbated ERS. Inhibiting the ERS response may be an attractive strategy to enhance the cardioprotective effects of postconditioning in diabetic patients.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China; The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China; The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: ay_guew_mz@163.com.
authors.forename: Erwei
authors.initials: E
authors.lastname: Gu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods*; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D010880:Piperidines; D000077208:Remifentanil
keywords: Endoplasmic reticulum stress; Hyperglycemia; Hypoxia/reoxygenation injury; Remifentanil postconditioning