Role of lipid peroxidation in tert-butylhydroperoxide-induced inhibition of endothelial cell calcium signaling.
Role of lipid peroxidation in tert-butylhydroperoxide-induced inhibition of endothelial cell calcium signaling.
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发表时间：
1993-03
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通讯作者：
S. J. Elliott;T. N. Doan;W. Schilling
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作者：
S. J. Elliott;T. N. Doan;W. Schilling
在小牛肺血管内皮细胞中，研究了膜渗透性氧化剂叔丁基过氧化氢（tert-buOOH）抑制Ca++信号转导的脂质过氧化作用的潜力。在10（-5）和10（-3）M浓度之间，氧化剂剂量依赖性地增加脂质过氧化作用，ED 50约为0.05 mM。此外，叔丁基OOH的作用在整个实验期间（3 h）具有时间依赖性。用21-氨基类固醇化合物21-[4-（5，6-双（二乙基氨基）-2-吡啶基）-1-哌嗪基]-16 α-甲基-孕-1，4，9（11）-三烯-3，20-二酮盐酸盐（U 74500 A）预孵育细胞，可将叔丁基OOH诱导的脂质过氧化降低至不可检测的水平。U 74500 A的作用具有剂量依赖性，IC 50约为10（-6）M。细胞与氨基类固醇的短暂孵育导致大于90%的抑制脂质过氧化作用，在随后的2小时孵育与叔丁氧醇和U 74500 A的治疗过程中与叔丁氧醇停止进一步的脂质过氧化作用。与此相反，含铁的部分，氯化血红素，加强叔丁基OOH对脂质过氧化的影响。当细胞在用叔丁基OOH处理之前用该试剂预孵育时，氯化血红素的ED 50约为10（-6）M。氯化血红素的增强作用是时间依赖性的，并达到接近最大值后，细胞孵育1小时之前，叔丁基OOH。在用氯化血红素和叔丁氧羰基处理前，用U 74500 A预孵育细胞，可使脂质过氧化反应降低75%。在加载有Ca（++）敏感性荧光指示剂fura-2的细胞中监测Ca++信号传导。（250字处删节）
The potential of lipid peroxidation in inhibition of Ca++ signaling by the membrane-permeant oxidant, tertiary butylhydroperoxide (tert-buOOH), was investigated in calf pulmonary vascular endothelial cells. The oxidant dose-dependently increased lipid peroxidation between concentrations of 10(-5) and 10(-3) M, with an ED50 of approximately 0.05 mM. In addition, the effect of tert-buOOH was time-dependent through the experimental period (3 h). Preincubation of cells with the 21-amino-steroid compound, 21-[4-(5,6-bis(diethylamino)-2-pyridinyl)-1-piperazinyl]-16 alpha-methyl-pregna-1,4,9(11)-triene-3,20-dione hydrochloride (U74500A), reduced tert-buOOH-induced lipid peroxidation to undetectable levels. The effect of U74500A was dose dependent with an IC50 of approximately 10(-6) M. Brief incubation of cells with the aminosteroid resulted in greater than 90% inhibition of lipid peroxidation during subsequent 2-h incubations with tert-buOOH and addition of U74500A during treatment of cells with tert-buOOH halted further lipid peroxidation. In contrast, the iron-containing moiety, hemin, potentiated the effect of tert-buOOH on lipid peroxidation. The ED50 of hemin was approximately 10(-6) M when cells were preincubated with this agent before treatment with tert-buOOH. The potentiating effect of hemin was time-dependent and reached a near maximum upon incubation of cells for 1 h before tert-buOOH. Preincubation of cells with U74500A before treatment with hemin and tert-buOOH decreased lipid peroxidation by 75%. Ca++ signaling was monitored in-cells loaded with the Ca(++)-sensitive fluorescent indicator, fura-2.(ABSTRACT TRUNCATED AT 250 WORDS)