Journal article
Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation: role of peroxynitrite formation
Apoptosis (London), Vol.11(8), pp.1453-1460
08/01/2006
DOI: 10.1007/s10495-006-7786-z
PMID: 16761110
Abstract
Objectives: Our previous study has shown that slow or "controlled" reperfusion for the ischemic heart reduces cardiomyocyte injury and myocardial infarction, while the mechanisms involved are largely unclear. In this study, we tested the hypothesis that enhancement of survival and prevention of apoptosis in hypoxic/reoxygenated cardiomyocytes by hypoxic postconditioning (HPC) are associated with the reduction in peroxynitrite (ONOO-) formation induced by hypoxia/reoxygenation (H/R). Methods: Isolated adult rat cardiomyocytes were exposed to 2 h of hypoxia followed by 3 h of reoxygenation. After 2 h of hypoxia the cardiomyocytes were either abruptly reperfused with pre-oxygenized culture medium or postconditioned by two cycles of 5 min of brief reoxygenation and 5 min of re-hypoxia followed by 160 min of abrupt reoxygenation. Results: H/R resulted in severe injury in cardiomyocytes as evidenced by decreased cell viability, increased LDH leakage in the culture medium, increased apoptotic index (P values all less than 0.01 vs. normoxia control group) and DNA ladder formation, which could be significantly attenuated by HPC treatment applied before the abrupt reoxygenation (P < 0.05 vs. H/R group). In addition, H/R induced a significant increase in ONOO- formation as determined by nitrotyrosine content in cardiomyocytes (P < 0.01 vs. normoxia control). Treatment with the potent ONOO(-)scavenger uric acid (UA) at reoxygenation significantly decreased ONOO(-)production and protected myocytes against H/R injury, whereas the same treatment with UA could not further enhance myocyte survival in HPC group (P > 0.05 vs. HPC alone). Statistical analysis showed that cell viability closely correlated inversely with myocyte ONOO- formation (P < 0.01). Conclusion: These data demonstrate that hypoxic postconditioning protects myocytes against apoptosis following reoxygenation and enhances myocytes survival, which is partly attributable to the reduced ONOO(-)formation following reoxygenation.
Details
- Title: Subtitle
- Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation: role of peroxynitrite formation
- Creators
- Hai-Chang Wang - Air Force Medical UniversityHai-Feng ZhangWen-Yi GuoHui Su - Air Force Medical UniversityKun-Ru Zhang - Air Force Medical UniversityQiu-Xia Li - Air Force Medical UniversityWenli YanXin L. Ma - Thomas Jefferson UniversityBernard L. Lopez - Thomas Jefferson UniversityTheodore A. Christopher - Thomas Jefferson UniversityFeng Gao - Air Force Medical University
- Resource Type
- Journal article
- Publication Details
- Apoptosis (London), Vol.11(8), pp.1453-1460
- Publisher
- Springer Nature
- DOI
- 10.1007/s10495-006-7786-z
- PMID
- 16761110
- ISSN
- 1360-8185
- eISSN
- 1573-675X
- Number of pages
- 8
- Grant note
- HL 63828 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01HL063828 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 08/01/2006
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359810602771
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