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  • Propofol Through Upregulating Caveolin-3 Attenuates Post-Hypoxic Mitochondrial Damage and Cell Death in H9C2 Cardiomyocytes During Hyperglycemia.

Propofol Through Upregulating Caveolin-3 Attenuates Post-Hypoxic Mitochondrial Damage and Cell Death in H9C2 Cardiomyocytes During Hyperglycemia.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (2017-11-14)
Fan Deng, Shuang Wang, Liangqing Zhang, Xiang Xie, Shuyun Cai, Haobo Li, Gui-Ling Xie, Hui-Lai Miao, Changmin Yang, Xin Liu, Zhengyuan Xia
ZUSAMMENFASSUNG

Hearts from diabetic subjects are susceptible to myocardial ischemia reperfusion (I/R) injury. Propofol has been shown to protect against myocardial I/R injury due to its antioxidant properties while the underlying mechanism remained incompletely understood. Thus, this study aimed to determine whether or not propofol could attenuate myocardial I/R injury by attenuating mitochondrial dysfunction/damage through upregulating Caveolin (Cav)-3 under hyperglycemia. Cultured rat cardiomyocyte H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in the absence or presence of propofol under high glucose (HG), and cell viability, lactate dehydrogenase (LDH) and mitochondrial viability as well as creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and intracellular adenosine triphosphate (ATP) content were measured with colorimetric Enzyme-Linked Immunosorbent Assays. Intracellular levels of oxidative stress was assessed using 2,7-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent staining and mitochondrial-dependent apoptosis was assessed by detecting mitochondrial membrane potential and the activation of apoptotic caspases 3 and 9. Exposure of cells to HG without or with H/R both significantly increased cell injury, cell apoptosis and enhanced oxidative stress that were associated with mitochondrial dysfunction and decreased Cav-3 protein expression. All these changes were further exacerbated following H/R under HG. Administration of propofol at concentrations from 12.5 to 50 µM but not 100 µM significantly attenuated H/R injury that was associated with increased Cav-3 expression and activation of the prosurvival proteins Akt and STAT3 with the optimal protective effects seen at 50 µM of propofol (P25). The beneficial effects of propofol(P25) were abrogated by Cav-3 disruption with β-methyl-cyclodextrin. Propofol counteracts cardiomyocyte H/R injury by attenuating mitochondrial damage and improving mitochondrial biogenesis through upregulating Cav-3 during hyperglycemia.

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Sigma-Aldrich
Monoclonal Anti-HIF-1 α antibody produced in mouse, clone ESEE122, 1 mg/mL, purified immunoglobulin
Sigma-Aldrich
Anti-CASP3 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-CAV3 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Caspase-9 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution