Effect of estradiol, diethylstilbestrol, and resveratrol on F0F1-ATPase activity from mitochondrial preparations of rat heart, liver, and brain

The question of whether estrogens or estrogen-like compounds would alter differentially the enzymatic activity of the F0F1-ATPase was addressed. Mitochondrial fractions of the liver, brain, and heart were obtained from adult male rats and solubilized by digitonin. About 85 % of the adenosine triphosphate hydrolysis by these three preparations come from the mitochondrial F0F1-ATPase. The enzymatic activity differed in the following order: liver < brain < heart. A concentration of 13 nM estradiol stimulated the F0F1-ATPase activity in heart by 10% (p < 0.01), but not in liver or brain. 17 beta -estradiol competed off the binding of estradiol-17 beta -17-(O-carboxymethyl)oxime:I-125- labeled bovine serium albumin to mitochondrial preparations of the heart, revealing two binding sites. Resveratrol inhibited the F0F1-ATPase activity in both heart and liver with an IC50 of 13-15 muM, which confirmed our previous report in preparations of brain. Lower doses (picomolar to nanomolar) of resveratrol stimulated the F0F1-ATPase activity in liver by 10% but not in heart. At 6.7 muM, diethylstilbestrol (DES) inhibited the F0F1-ATPase activity in the three preparations by 61-67%. This study demonstrates that estradiol activates rat heart mitochondrial F0F1-ATPase at physiologic concentrations and that the F0F1-ATPase activity is markedly different in rat liver, brain, and heart. In addition, estradiol, DES, and resveratrol alter the F0F1-ATPase activity selectively, probably via different mechanisms.