Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion

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

*Corresponding author for this work

Research output: Contribution to journalArticle

278 Scopus citations

Abstract

Cardiomyocyte death after ischemia/reperfusion correlates with oxidant stress, and antioxidants confer protection in that model. Preconditioning (PC) with hypoxia or adenosine also confers protection, leading us to hypothesize that PC protects by attenuating oxidant generation during subsequent ischemia/reperfusion. Chick cardiomyocytes were preconditioned with 10 minutes of hypoxia or adenosine (100 μmol/L), followed by 1 hour of simulated ischemia and 3 hours of reperfusion. Adenosine PC decreased cell death from 50±3% to 18±4% and enhanced the return of contractions during reperfusion, as observed previously with hypoxic PC. A transient burst of dichlorofluorescein (sensitive to H2O2) oxidation that was significantly attenuated by PC initiated by hypoxia or adenosine was seen at reperfusion. The protein kinase C (PKC) inhibitor Go-6976 and the mitochondrial ATP- sensitive K+ (K(ATP)) channel inhibitor 5-hydroxydecanoate each abolished protection and abrogated the PC-induced attenuation of reperfusion oxidant stress. By contrast, when given only at reperfusion, the K+ channel opener pinacidil or the antioxidants 2-mercaptopropionylglycine and 1,10- phenanthroline decreased oxidant stress at reperfusion and improved survival and return of contractions. Thus, PC protection is associated with an attenuation of the oxidant burst at reperfusion, regardless of the method by which PC is triggered. Loss of PC protection associated with PKC inhibition or K(ATP) channel inhibitors is associated with a restoration of that oxidant stress. These results suggest a mechanism for PC protection and reveal a functional link between PKC activation and K(ATP) channel activation in that pathway.

Original languageEnglish (US)
Pages (from-to)541-548
Number of pages8
JournalCirculation research
Volume86
Issue number5
DOIs
StatePublished - Mar 17 2000

Keywords

  • Hydrogen peroxide
  • K(ATP) channels
  • Protein kinase C
  • Reactive oxygen species
  • Reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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