Effective pharmacotherapy against oxidative injury: Alternative utility of an ATP-sensitive potassium channel opener

Cevher Ozcan, Andre Terzic, Martin Bienengraeber

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Cardiomyocyte viability following ischemia-reperfusion critically depends on mitochondrial function. In this regard, potassium channel openers (KCOs) targeting mitochondria have emerged as powerful cardioprotective agents when applied at the onset of ischemia. However, it is controversial whether openers are still protective when applied at the onset of reoxygenation. Here, H9c2 cardiomyocytes and mitochondria isolated from the rat heart ventricle were subjected to ischemia-reoxygenation or oxidative stress in the absence or presence of 100 μM diazoxide, a potassium channel opener. Ischemia-reoxygenation or oxidative stress significantly reduced cell viability, induced structural damage in association with increased mitochondrial protein release, and impaired oxidative phosphorylation. However, treatment with diazoxide before anoxia or at the onset of reoxygenation, as well as during oxidative stress, prevented cell death and mitochondrial dysfunction and preserved cellular and mitochondrial structural integrity. These protective effects were blocked by 5-hydroxydecanoate. Thus, treatment with potassium channel openers even at the time of reoxygenation may provide a significant protection of the myocardium. The protective mechanism is at least in part endogenous to the mitochondria because protection was also observed in isolated mitochondria.

Original languageEnglish (US)
Pages (from-to)411-418
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume50
Issue number4
DOIs
StatePublished - Oct 1 2007

Keywords

  • Cell survival
  • Diazoxide
  • H O
  • Mitochondrial function
  • Oxidative stress
  • Reactive oxygen species
  • Reoxygenation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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