Late ischemic preconditioning is mediated in myocytes by enhanced endogenous antioxidant activity stimulated by oxygen-derived free radicals

Xiaolin Zhai, Xiaobo Zhou, Muhammad Ashraf

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The primary objective of the study was to test the hypothesis that oxygen radical during initial anoxia stimulate endogenous antioxidant activity in late preconditioning in myocytes. Isolated rat myocytes were preconditioned in one group with two cycles of 5 minutes of anoxia and 5 minutes of reoxygenation and in another group with exogenous superoxide anion (·O2-) generated by reaction of xanthine oxidase with xanthine. Myocytes were kept for 24 hours, after which they were exposed to 60 minutes of anoxia and 60 minutes of reoxygenation. Preconditioned myocytes exhibited decreased LDH release, reduced malondialdehyde formation, increased cell viability, and well-preserved cell structure. ·O2- production was increased in myocytes immediately after treatment with repetitive anoxia (1.65 ± 0.08 nmol/mg protein) or exogenous ·O2- (1.42 ± 0.11 nmol/mg protein). Allopurinol, a xanthine oxidase inhibitor, abolished ·O2- production during the initial preconditioning period. Twenty-four hours later, Mn SOD activity declined in anoxic control myocytes (0.38 ± 0.06 U/mg protein), whereas it increased significantly in myocytes preconditioned with repetitive anoxia (3.25 ± 0.15 nmol/mg protein) or with exogenous ·O2- (2.27 ± 0.10 nmol/mg protein). The increase in Mn SOD activity and myocardial protective effects observed in preconditioned myocytes were totally blocked by allopurinol. These results indicate that oxygen radicals generated during the initial preconditioning period activate endogenous antioxidant defense (increased Mn SOD activity) 24 hours later, which contributes to the late cardioprotection of preconditioning.

Original languageEnglish (US)
Pages (from-to)156-166
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume793
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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