Generation of superoxide in cardiomyocytes during ischemia before reperfusion

Lance B. Becker*, Terry L. Vanden Hoek, Zuo Hui Shao, Chang Qing Li, Paul T. Schumacker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

370 Scopus citations

Abstract

Although a burst of oxidants has been well described with reperfusion, less is known about the oxidants generated by the highly reduced redox state and low O2 of ischemia. This study aimed to further identify the species and source of these oxidants. Cardiomyocytes were exposed to 1 h of simulated ischemia while oxidant generation was assessed by intracellular dihydroethidine (DHE) oxidation. Ischemia increased DHE oxidation significantly (0.7 ± 0.1 to 2.3 ± 0.3) after 1 h. Myxothiazol (mitochondrial site III inhibitor) attenuated oxidation to 1.3 ± 0.1, as did the site I inhibitors rotenone (1.0 ± 0.1), amytal (1.1 ± 0.1), and the flavoprotein oxidase inhibitor diphenyleneiodonium (0.9 ± 0.1). By contrast, the site IV inhibitor cyanide, as well as inhibitors of xanthine oxidase (allopurinol), nitric oxide synthase (nitro-L-arginine methyl ester), and NADPH oxidase (apocynin), had no effect. Finally, DHE oxidation increased with Cu- and Zn-containing superoxide dismutase (SOD) inhibition using diethyldithiocarbamate (2.7 ± 0.1) and decreased with exogenous SOD (1.1 ± 0.1). We conclude that significant superoxide generation occurs during ischemia before reperfusion from the ubisemiquinone site of the mitochondrial electron transport chain.

Original languageEnglish (US)
Pages (from-to)H2240-H2246
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number6 46-6
DOIs
StatePublished - Dec 1999

Keywords

  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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