Ca2+ concentrations are key determinants of ischemia-reperfusion-induced apoptosis: significance for the molecular mechanism of Bcl-2 action.
The mechanism of action of the anti-apoptotic oncogene Bcl-2 and Ca2+ regulation in ischemia-reperfusion injury is still obscure. In this present study, we investigated mitochondrial Ca2+ overloads and mechanism of action of Bcl-2. Eighteen Wistar rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), and amlodipine-treated group (1 mg kg(-1) body weight/daily by oral route for 7 days before inducing ischemia-reperfusion maneuver) (III) (n = 6). Rats were subjected to 1 h of hepatic ischemia followed by 3-h reperfusion. Mitochondrial Ca2+ content was determined and damage was confirmed by transmission electron microscopy. Decrease of mitochondrial Ca2+ level is related to reduction of apoptosis and cellular changes, viz. increased Bcl-2 expression followed by reduction in secondary endoplasmic reticulum, whereas ischemia/reperfusion group shows overloading Ca2+ ions and decrease in Bcl-2 expression as compared to sham-operated rats. Thus, Bcl-2-dependent reduction of Ca2+ is an important component of the anti-apoptotic program in ischemia-reperfusion injury.
Chattopadhyay
Pronobesh
P
College of Pharmacy, IFTM, Lodhipur Rajput, Moradabad 244001, India. chatto_pronobesh@rediffmail.com
Chaudhury
Pallab
P
Wahi
Arun Kumar
AK
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D002118:Calcium