title: Anti-oxidant effects of estrogen reduce [Ca2+]i during metabolic inhibition.
abstract: We previously reported that 17beta-estradiol (betaE2) inhibits the rise in [Ca(2+)](i) and [Na(+)](i) during metabolic inhibition (MI) in mouse cardiomyocytes, but the mechanism has not yet been clarified. Estrogen has been reported to have anti-oxidant properties. We, therefore, have investigated whether interaction with the estrogen receptor (ER) is involved, or whether estrogen reduces free-radical-induced impairment of Na(+)-K(+) ATPase in cardiac myocytes, and whether this effect reduces [Ca(2+)](i) rise. Male mouse ventricular myocytes were studied. Flow cytometry was used with fluo-3 for [Ca(2+)](i) measurement. Dead cells were excluded from analysis by propidium iodide fluorescence. betaE2 reduced the increase in [Ca(2+)](i) during MI even in the presence of the ER blocker tamoxifen. A similar effect on [Ca(2+)](i) was produced by its non-estrogenic isomer, betaE2-estradiol. Other hormones (estrone and estriol) with a phenolic structure also inhibited Ca(2+) overload during MI, but testosterone without the structure did not. The betaE2 effect was attenuated by inhibition of Na(+)-Ca(2+) exchanger (KB-R7943) or Na(+)-K(+) ATPase (low K(+) or ouabain), but not by block of L-type Ca(2+) channel (nifedipine). Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid), a superoxide scavenger, decreased the rise in [Ca(2+)](i) and abolished the betaE2 effect during MI. We conclude that the acute cardioprotective effect of estrogen during MI may be mediated by an ER-independent anti-oxidant action, which results in improved function of Na(+)-K(+) ATPase.
authors.affiliation: Division of Cardiology, University of Utah Health Sciences Center, 50 N Medical Drive, Salt Lake City, UT 84132, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sugishita
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: W H
authors.initials: WH
authors.lastname: Barry
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000502:physiology; D004964:Estriol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D004970:Estrone; D013739:Testosterone; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D004964:Estriol; D009543:Nifedipine