Ischemic preconditioning attenuates apoptosis through protein kinase C in rat hearts.
To investigate the role of protein kinase C (PKC) in the mechanism of ischemic preconditioning (IP), infarct size and the incidence of apoptosis caused by ischemia-reperfusion were tested in four groups of Sprague-Dawley rats. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/ml) was administered 5 min before the 30-min coronary occlusion followed by a 6-h reperfusion. Three cycles of 3 min of ischemia followed by 3 min of reperfusion was performed as IP before the 30-min ischemia followed by a 6-h reperfusion with or without calphostin C pretreatment. Infarct size defined by triphenyltetrazolium chloride staining was reduced from 60 +/- 2 to 26 +/- 2% by IP (P < 0.01), but the effect of IP was abolished by calphostin C (51 +/- 3%). Apoptosis defined by in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL) was reduced by IP from 44 +/- 3 to 13 +/- 2% in the subendocardial region (P < 0.01). This effect of IP was abolished by calphostin C (42 +/- 8%). Thus the effect of IP on reducing the infarct size and the incidence of apoptosis are both mediated by PKC in rat hearts.
Okamura
T
T
The Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube 755-8505, Japan.
Miura
T
T
Iwamoto
H
H
Shirakawa
K
K
Kawamura
S
S
Ikeda
Y
Y
Iwatate
M
M
Matsuzaki
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002467:Cell Nucleus / Q000502:physiology; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D006439:Hemodynamics; D020287:In Situ Nick-End Labeling; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011493:Protein Kinase C