Tributyltin-induced Ca(2+) mobilization via L-type voltage-dependent Ca(2+) channels in PC12 cells.
Tributyltin-induced Ca(2+) mobilization via L-type voltage-dependent Ca(2+) channels in PC12 cells.
复制标题
PC12 细胞中三丁基锡通过 L 型电压依赖性 Ca(2) 通道诱导 Ca(2) 动员。
DOI：
10.1016/j.etap.2009.02.006
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发表时间：
2009
影响因子：
4.3
通讯作者：
Komori,Seiichi
中科院分区：
文献类型：
--
作者：
Unno,Toshihiro;Iida,Ryoko;Okawa,Masashi;Matsuyama,Hayato;Hossain,MuhammadMubarak;Kobayashi,Haruo;Komori,Seiichi
研究了三丁基锡（TBT）对神经生长因子（NGF）诱导分化的PC 12细胞胞浆内Ca ~（2+）浓度（[Ca ~（2+）]c）和细胞活力的影响。TBT浓度依赖性地增加[Ca ~（2+）] c，EC_（50）值为0.07μM。这种效果显着降低细胞外Ca 2+或膜去极化与高K+介质的去除，但不受毒胡萝卜素引起细胞内Ca 2+商店耗尽。L型电压依赖性钙通道（VDCC）阻断剂尼卡地平可阻断TBT的作用，而N型VDCC阻断剂ω-芋螺毒素则无此作用。TBT降低活细胞数，EC 50值为0.09μM。尼卡地平或BAPTA-AM螯合胞浆Ca ~（2+）可阻止TBT诱导的细胞死亡，ω-芋螺毒素则不能阻止TBT诱导的细胞死亡。结果表明，TBT通过激活L型VDCCs引起细胞内[Ca ~（2+）] c升高，支持了有机锡诱导的细胞死亡是通过L型VDCCs的Ca ~（2+）动员引起的。
The effects of tributyltin (TBT) on cytosolic Ca2+concentration ([Ca2+]c) and cell viability were investigated in nerve growth factor-differentiated PC12 cells. TBT concentration dependently increased [Ca2+]cwith an EC50value of 0.07μM. This effect was markedly reduced by removal of the extracellular Ca2+or membrane depolarization with a high K+medium, but unaffected by thapsigargin causing depletion of intracellular Ca2+stores. The L-type voltage-dependent Ca2+channel (VDCC) blocker nicardipine blocked the effect of TBT, but the N-type VDCC blocker ω-conotoxin did not. TBT decreased the number of viable cells with an EC50value of 0.09μM. The TBT-induced cell death was prevented by nicardipine or by chelating the cytosolic Ca2+with BAPTA-AM, but not by ω-conotoxin. The results show that TBT causes an increase in [Ca2+]cvia activating L-type VDCCs, and support the idea that the organotin-induced cell death arises through Ca2+mobilization via L-type VDCCs.