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
SN - 0160-2446
VL - 50
SP - 411
EP - 418
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 4
ER -