Participation of caspase-3-like protease in necrotic cell death of myocardium during ischemia-reperfusion injury in rat hearts.
This experimental study was designed to determine if caspase-3-like protease is activated during a short period of ischemia - reperfusion (I-R) that did not induce apoptosis, and whether protease-3-protease inhibitor could prevent myocardial I-R injury, especially necrotic cell death. The subjects were 20 isolated rat hearts; 10 were pretreated for 20 min with 100 micromol/L of the protease-3-protease inhibitor, peptide antagonist Asp-Glu-Val-Asp-CHO (DEVD) (Group D), and compared with the 10 no-pretreated hearts (Group C). The hearts were then subjected to 20, 30, 45, and 60 min of normothermic global ischemia followed by 30 min of reperfusion. Caspase-3-like protease was significantly elevated after 45 min and 60 min in ischemic hearts. Group D had reduced levels of caspase-3-like protease activity after 45 min and 60 min (302+/-58%, 378+/-69% of pre-ischemic control, respectively), as compared with Group C (542+/-74%, 689+/-85%, respectively) (p<0.05, p<0.05, respectively). Histological analysis also demonstrated a decrease in cellular damage in Group D, as the count ratio of necrotic cells with total cardiomyocytes was 38%, as compared with 78% in the control group (p<0.05). Caspase-3-like protease participated in I-R injury in rat hearts and inhibition of this protease resulted in a reduction of necrotic cell death.
Naka
Yoshihisa
Y
Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Suita, Japan.
Sawa
Yoshiki
Y
Nishimura
Motonobu
M
Hirata
Nobuaki
N
Ueda
Hideki
H
Ohtake
Shigeaki
S
Matsuda
Hikaru
H
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D010450:Endopeptidases / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology*; D016277:Ventricular Function, Left
D010450:Endopeptidases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases