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 FOF1-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 FOF1-ATPase. The enzymatic activity differed in the following order: liver < brain < heart. A concentration of 13 nM estradiol stimulated the FOF1-ATPase activity in heart by 10% (p < 0.01), but not in liver or brain. 17beta-estradiol competed off the binding of estradiol-17beta-17-(O-carboxymethyl)oxime:125I-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 microM, which confirmed our previous report in preparations of brain. Lower doses (picomolar to nanomolar) of resveratrol stimulated the FOF1-ATPase activity in liver by 10% but not in heart. At 6.7 microM, diethylstilbestrol (DES) inhibited the FOF1-ATPase activity in the three preparations by 61-67%. This study demonstrates that estradiol activates rat heart mitochondrial FOF1-ATPase at physiologic concentrations and that the FOF1-ATPase activity is markedly different in rat liver, brain, and heart. In addition, estradiol, DES, and resveratrol alter the FOF1-ATPase activity selectively, probably via different mechanisms.
Kipp
J L
JL
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana 61801, USA. liu4@uiuc.edu
Ramirez
V D
VD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology / Q000648:ultrastructure; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004072:Digitonin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006868:Hydrolysis; D007457:Iodine Radioisotopes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D008929:Mitochondria, Heart / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012995:Solubility; D013267:Stilbenes / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D013267:Stilbenes; D012710:Serum Albumin, Bovine; D004958:Estradiol; D004054:Diethylstilbestrol; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D011770:Pyruvate Kinase; D006180:Proton-Translocating ATPases; D004072:Digitonin; D000077185:Resveratrol