Ca+2 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 Ca+2 regulation in ischemia–reperfusion injury is still obscure. In this present study, we investigated mitochondrial Ca+2 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 Ca+2 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 Ca+2 ions and decrease in Bcl-2 expression as compared to sham-operated rats. Thus, Bcl-2-dependent reduction of Ca+2 is an important component of the anti-apoptotic program in ischemia–reperfusion injury.