Reductant substrate for glutathione peroxidase modulates oxidant inhibition of Ca2+ signaling in endothelial cells.
Reductant substrate for glutathione peroxidase modulates oxidant inhibition of Ca2+ signaling in endothelial cells.
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谷胱甘肽过氧化物酶的还原底物调节内皮细胞中 Ca2 信号传导的氧化抑制。
DOI：
10.1152/ajpheart.1995.268.1.h278
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Henschke,PN
中科院分区：
文献类型：
--
作者：
Elliott,SJ;Doan,TN;Henschke,PN
叔丁基过氧化氢 (t-BOOH) 介导的氧化应激可抑制培养内皮细胞中激动剂刺激的 Ca2+ 进入和内部储存 Ca2+ 释放。在用丁硫氨酸-[S,R]-亚砜亚胺 (BSO)（一种 γ-谷氨酰半胱氨酸合成酶抑制剂）或 1-氯-2,4-二硝基苯 (CDNB)（谷胱甘肽-S-转移酶的共底物）预孵育的细胞中，确定了细胞内谷胱甘肽在调节氧化应激对 Ca2+ 信号传导的影响中的作用。 BSO 和 CDNB 分别使内皮细胞谷胱甘肽含量降低 85% 和 97%（对照谷胱甘肽，21.5 +/- 2.3 nmol/mg 蛋白质）。每种药物都加速了 t-BOOH 对装载 fura 2 的细胞中 Ca2+ 信号传导的时间依赖性影响，并增强了对 t-BOOH 诱导的缓激肽刺激的 45Ca2+ 流出的抑制作用。这些结果表明，还原型谷胱甘肽（谷胱甘肽过氧化物酶的主要共底物）的可用性降低，增强了氢过氧化物氧化应激对受体操纵的 Ca2+ 跨质膜进入和内部储存的 Ca2+ 释放的影响。目前的研究结果表明，细胞内谷胱甘肽可用性和/或谷胱甘肽氧化还原循环活性是Ca(2+)依赖性信号转导的氧化剂抑制的极其重要的调节剂。
Oxidant stress mediated by tert-butyl hydroperoxide (t-BOOH) inhibits agonist-stimulated Ca2+ entry and internal store Ca2+ release in cultured endothelial cells. The role of intracellular glutathione in modulating the effects of oxidant stress on Ca2+ signaling was determined in cells preincubated with buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, or 1-chloro-2,4-dinitrobenzene (CDNB), a cosubstrate for glutathione-S-transferase. BSO and CDNB decreased endothelial cell glutathione content by 85 and 97%, respectively (control glutathione, 21.5 +/- 2.3 nmol/mg protein). Each agent accelerated the time-dependent effects of t-BOOH on Ca2+ signaling in fura 2-loaded cells and potentiated the inhibition of bradykinin-stimulated 45Ca2+ efflux induced by t-BOOH. These results indicate that decreased availability of reduced glutathione, the primary cosubstrate for glutathione peroxidase, potentiates the effect of hydroperoxide oxidant stress on receptor-operated Ca2+ entry across the plasmalemma and Ca2+ release from internal stores. The present findings suggest that intracellular glutathione availability and/or glutathione redox cycle activity are critically important modulators of oxidant inhibition of Ca(2+)-dependent signal transduction.