Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload
| Autor: | Ning-Ping Wang, He-Ying Sun, Zhi-Qing Zhao, Jakob Vinten-Johansen, Robert A. Guyton, Faraz Kerendi, Hajime Kin, Michael E. Halkos |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cell Survival
Physiology Myocardial Reperfusion Injury Cell Communication In Vitro Techniques Pharmacology Biology Lipid peroxidation chemistry.chemical_compound Superoxides Malondialdehyde Physiology (medical) medicine Animals Myocytes Cardiac Propidium iodide Rats Wistar Hypoxia Cells Cultured Cardioprotection chemistry.chemical_classification Reactive oxygen species L-Lactate Dehydrogenase Superoxide Dismutase Cytochromes c Hydrogen Peroxide Hypoxia (medical) Rats Biochemistry chemistry Ischemic Preconditioning Myocardial Luminescent Measurements Ischemic preconditioning Calcium medicine.symptom Reactive Oxygen Species Cardiology and Cardiovascular Medicine Intracellular |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 288:H1900-H1908 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | We have shown that intermittent interruption of immediate reflow at reperfusion (i.e., postconditioning) reduces infarct size in in vivo models after ischemia. Cardioprotection of postconditioning has been associated with attenuation of neutrophil-related events. However, it is unknown whether postconditioning before reoxygenation after hypoxia in cultured cardiomyocytes in the absence of neutrophils confers protection. This study tested the hypothesis that prevention of cardiomyocyte damage by hypoxic postconditioning (Postcon) is associated with a reduction in the generation of reactive oxygen species (ROS) and intracellular Ca2+ overload. Primary cultured neonatal rat cardiomyocytes were exposed to 3 h of hypoxia followed by 6 h of reoxygenation. Cardiomyocytes were postconditioned after the 3-h index hypoxia by three cycles of 5 min of reoxygenation and 5 min of rehypoxia applied before 6 h of reoxygenation. Relative to sham control and hypoxia alone, the generation of ROS (increased lucigenin-enhanced chemiluminescence, SOD-inhibitable cytochrome c reduction, and generation of hydrogen peroxide) was significantly augmented after immediate reoxygenation as was the production of malondialdehyde, a product of lipid peroxidation. Concomitant with these changes, intracellular and mitochondrial Ca2+ concentrations, which were detected by fluorescent fluo-4 AM and X-rhod-1 AM staining, respectively, were elevated. Cell viability assessed by propidium iodide staining was decreased consistent with increased levels of lactate dehydrogenase after reoxygenation. Postcon treatment at the onset of reoxygenation reduced ROS generation and malondialdehyde concentration in media and attenuated cardiomyocyte death assessed by propidium iodide and lactate dehydrogenase. Postcon treatment was associated with a decrease in intracellular and mitochondrial Ca2+ concentrations. These data suggest that Postcon treatment reduces reoxygenation-induced injury in cardiomyocytes and is potentially mediated by attenuation of ROS generation, lipid peroxidation, and intracellular and mitochondrial Ca2+ overload. |
| Databáze: | OpenAIRE |
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