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Effect of the organotin compound triethyltin on Ca2+ handling in human prostate cancer cells.

机译:有机锡化合物三乙锡对人前列腺癌细胞中Ca2 +处理的影响。

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The effects of triethyltin on Ca2+ mobilization in human PC3 prostate cancer cells have been explored. Triethyltin increased [Ca2+]i at concentrations larger than 3 microM with an EC50 of 30 microM. Within 5 min, the [Ca2+]i signal was composed of a gradual rise and a sustained phase. The [Ca2+]i signal was reduced by half by removing extracellular Ca2+. The triethyltin-induced [Ca2+]i increases were inhibited by 40% by 10 microM nifedipine, nimodipine and nicardipine, but were not affected by 10 microM of verapamil or diltiazem. In Ca2+-free medium, pretreatment with thapsigargin (1 microM), an endoplasmic reticulum Ca+ pump inhibitor, reduced 200 microM triethyltin-induced Ca+ increases by 50%. Pretreatment with U73122 (2 microM) to inhibit phospholipase C did not alter 200 microM triethyltin-induced [Ca2+]i increases. Incubation with triethyltin at a concentration that did not increase [Ca2+]i (1 microM) in Ca2+-containing medium for 3 min potentiated ATP (10 microM)- or bradykinin (1 microLM)-induced [Ca2+]i increases by 41 +/- 3% and 51 +/- 2%, respectively. Collectively, this study shows that the environmental toxicant triethyltin altered Ca2+ handling in PC3 prostate cancer cells in a concentration-dependent manner: at higher concentrations it increased basal [Ca2+]i; and at lower concentrations it potentiated agonists-induced [Ca2+]i increases.
机译:已经研究了三乙基锡对人PC3前列腺癌细胞中Ca2 +动员的影响。三乙基锡在大于3 microM的浓度下增加[Ca2 +] i,EC50为30 microM。在5分钟内,[Ca2 +] i信号由逐渐上升和持续的相位组成。通过去除细胞外Ca2 +,[Ca2 +] i信号减少了一半。三乙基锡诱导的[Ca2 +] i增加被10 microM的硝苯地平,尼莫地平和尼卡地平抑制了40%,但不受10 microM的维拉帕米或地尔硫卓的影响。在不含Ca2 +的培养基中,用thapsigargin(1 microM)(一种内质网Ca +泵抑制剂)进行预处理,可使200 microM三乙基锡诱导的Ca +减少50%。用U73122(2 microM)进行预处理以抑制磷脂酶C不会改变200 microM三乙基锡诱导的[Ca2 +] i增加。与三乙基锡的孵育不会在含Ca2 +的培养基中增加[Ca2 +] i(1 microM)3分钟,而增强的ATP(10 microM)-或缓激肽(1 microLM)诱导的[Ca2 +] i则增加41 + / -分别为3%和51 +/- 2%。总体而言,这项研究表明,环境有毒物质三乙锡以浓度依赖的方式改变了PC3前列腺癌细胞中Ca2 +的处理:在较高浓度下,它会增加基础[Ca2 +] i。在较低的浓度下,它会增强激动剂诱导的[Ca2 +] i。

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