College of Life Sciences, Graduate University of Chinese Academy of Sciences, Yuquan Road 19(A), 100049 Beijing, China.
Eur J Pharmacol. 2010 Jan 25;626(2-3):276-82. doi: 10.1016/j.ejphar.2009.09.034. Epub 2009 Sep 24.
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.
血液中组胺水平升高在动脉粥样硬化的发病机制中起作用。钙信号转导介导内皮细胞中组胺的作用。硒（Se）是人体必需的微量元素。不同氧化态的硒化合物被发现对 ECV304 细胞系中组胺诱导的钙信号具有相反的作用。正如我们之前的论文中所报道的，当以亚硒酸钠的形式添加 Se 时，组胺 H（1）-受体的反应性增加。我们在这里表明，作为培养补充剂，亚硒酸钠增强了硒蛋白谷胱甘肽还原酶（TrxR）的活性以及对组胺刺激的钙反应，用金硫葡萄糖处理细胞可逆转这种反应，金硫葡萄糖是一种亲核药物，可选择性修饰硫醇/硒醇基团。亚硒酸钠很可能通过增加 TrxR 活性引起巯基/二硫键氧化还原平衡的还原偏移。相比之下，当细胞用形式为 ebselen 的 Se 处理时，一种具有过氧化物酶样活性的硫醇氧化剂，组胺诱导的钙释放和钙内流显著受到抑制。这种作用似乎与硫醇定向修饰有关，而不是 ebselen 的过氧化物酶样活性，因为增加细胞过氧化物酶活性并不能复制这种抑制作用。因此，亚硒酸钠和 ebselen 对组胺诱导的钙信号的相反作用至少部分是通过它们在调节巯基/二硫键氧化还原状态方面的相反作用来实现的。
