Opposing regulation of histamine-induced calcium signaling by sodium selenite and ebselen via alterations of thiol redox status.
Elevated blood histamine plays a role in the pathogenesis of atherosclerosis. Calcium signaling mediates histamine action in endothelial cells. Selenium (Se) is a dietary essential trace element for humans. Se compounds in different oxidation states were found to exhibit an opposing effect on the histamine-induced calcium signaling in the ECV304 cell line. When Se in the form of sodium selenite was added in the cell culture, the reactivity of the histamine H(1)-receptor was increased as reported in our previous paper. We here show that as a culture supplement, sodium selenite enhanced the activity of selenoprotein thioredoxin reductase (TrxR) and the calcium response to histamine stimulation, which were reversed by treating the cells with gold thioglucose, a nucleophilic drug that selectively modifies thiolate/selenolate groups. Sodium selenite most likely caused a reductive shift in the thiol/disulfide redox balance through increasing TrxR activity. In contrast, when the cells were treated with Se in the form of ebselen, a thiol oxidant with peroxidase-like activity, histamine-induced calcium release and calcium entry were significantly suppressed. This effect appeared related to the thiol-directed modification rather than the peroxidase-like activity of ebselen, because this inhibitory effect was not replicated by increasing cellular peroxidase activity. Thus, the opposing effects of sodium selenite and ebselen on histamine-induced calcium signaling are achieved, at least in part, through their opposite actions in modulating the thiol/disulfide redox state.
College of Life Sciences, Graduate University of Chinese Academy of Sciences, Yuquan Road 19(A), 100049 Beijing, China.
Huihui
H
Zhang
Liangwei
L
Zhong
D000818:Animals; D001393:Azoles / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D004220:Disulfides / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism; D018038:Sodium Selenite / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D001393:Azoles; D004220:Disulfides; D054833:Isoindoles; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D011969:Receptors, Histamine H1; D013438:Sulfhydryl Compounds; C042986:ebselen; D006632:Histamine; D018038:Sodium Selenite