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 di fferentially the enzymatic activity of the F0F1-ATPase was addressed. Mitoc hondrial fractions of the liver, brain, and heart were obtained from adult male rats and solubilized by digitonin. About 85 % of the adenosine triphos phate hydrolysis by these three preparations come from the mitochondrial F0 F1-ATPase. The enzymatic activity differed in the following order: liver < brain < heart. A concentration of 13 nM estradiol stimulated the F0F1-ATPas e 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-carboxymethy l)oxime:I-125- labeled bovine serium albumin to mitochondrial preparations of the heart, revealing two binding sites. Resveratrol inhibited the F0F1-A TPase activity in both heart and liver with an IC50 of 13-15 muM, which con firmed 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 demon strates that estradiol activates rat heart mitochondrial F0F1-ATPase at phy siologic concentrations and that the F0F1-ATPase activity is markedly diffe rent in rat liver, brain, and heart. In addition, estradiol, DES, and resve ratrol alter the F0F1-ATPase activity selectively, probably via different m echanisms.