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

21 Citations (Scopus)

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 2007

Fingerprint

KATP Channels
Potassium Channels
Mitochondria
Ischemia
Diazoxide
Drug Therapy
Oxidative Stress
Wounds and Injuries
Cardiac Myocytes
Cardiotonic Agents
Mitochondrial Proteins
Oxidative Phosphorylation
Reperfusion
Heart Ventricles
Cell Survival
Myocardium
Cell Death
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Effective pharmacotherapy against oxidative injury : Alternative utility of an ATP-sensitive potassium channel opener. / Ozcan, Cevher; Terzic, Andre; Bienengraeber, Martin.

In: Journal of Cardiovascular Pharmacology, Vol. 50, No. 4, 10.2007, p. 411-418.

Research output: Contribution to journalArticle

@article{47d5660bc9d24b68a0dcb4bfb7deb2e7,
title = "Effective pharmacotherapy against oxidative injury: Alternative utility of an ATP-sensitive potassium channel opener",
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.",
keywords = "Cell survival, Diazoxide, H O, Mitochondrial function, Oxidative stress, Reactive oxygen species, Reoxygenation",
author = "Cevher Ozcan and Andre Terzic and Martin Bienengraeber",
year = "2007",
month = "10",
doi = "10.1097/FJC.0b013e31812378df",
language = "English (US)",
volume = "50",
pages = "411--418",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Effective pharmacotherapy against oxidative injury

T2 - Alternative utility of an ATP-sensitive potassium channel opener

AU - Ozcan, Cevher

AU - Terzic, Andre

AU - Bienengraeber, Martin

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

KW - Cell survival

KW - Diazoxide

KW - H O

KW - Mitochondrial function

KW - Oxidative stress

KW - Reactive oxygen species

KW - Reoxygenation

UR - http://www.scopus.com/inward/record.url?scp=37349022807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37349022807&partnerID=8YFLogxK

U2 - 10.1097/FJC.0b013e31812378df

DO - 10.1097/FJC.0b013e31812378df

M3 - Article

C2 - 18049309

AN - SCOPUS:37349022807

VL - 50

SP - 411

EP - 418

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 4

ER -