Comparative sensitivity of rat cerebellar neurons to dysregulation of divalent cation homeostasis and cytotoxicity caused by methylmercury
Comparative sensitivity of rat cerebellar neurons to dysregulation of divalent cation homeostasis and cytotoxicity caused by methylmercury
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DOI：
10.1016/j.taap.2005.02.015
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发表时间：
2005-11-01
影响因子：
3.8
通讯作者：
Atchison, WD
中科院分区：
文献类型：
--
作者：
Edwards, JR;Marty, MS;Atchison, WD
本研究的目的是确定甲基汞（MeHg）的相对有效性，改变二价阳离子的稳态，并导致细胞死亡的MeHg-抗性小脑浦肯野和MeHg-敏感的颗粒神经元。应用0.5-5 μ M的甲基汞浦肯野细胞和颗粒细胞培养引起的浓度和时间依赖性的双相增加Fura-2荧光。在0.5和1 μ M的甲基汞，升高的fura-2荧光诱导的甲基汞是双相的两种细胞类型，但显着延迟在浦肯野相比，颗粒细胞。应用的重金属螯合剂，TPEN，浦肯野细胞引起的Fura-2荧光信号的比例急剧下降，表明甲基汞导致释放的Ca 2+和非Ca 2+二价阳离子。浦肯野细胞也比颗粒细胞更耐甲基汞的神经毒性作用。在24.5 μ M甲基汞后，97.7%的浦肯野细胞存活。在3 μ M甲基汞，没有检测到浦肯野细胞活力的损失。相反，只有40.6%的小脑颗粒细胞存活24.5小时后，应用3 μ M甲基汞。总之，浦肯野神经元在原代培养似乎是更耐甲基汞引起的失调二价阳离子稳态和随后的细胞死亡时，小脑颗粒细胞相比。在浦肯野神经元中，甲基汞释放的非Ca ~（2+）二价阳离子有重要的成分。(c)2005年爱思唯尔公司All rights reserved.
The objective of the present study was to determine the relative effectiveness of methylmercury (MeHg) to alter divalent cation homeostasis and cause cell death in MeHg-resistant cerebellar Purkinje and MeHg-sensitive granule neurons. Application of 0.5-5 mu M MeHg to Purkinje and granule cells grown in culture caused a concentration- and time-dependent biphasic increase in fura-2 fluorescence. At 0.5 and 1 mu M MeHg, the elevations of fura-2 fluorescence induced by MeHg were biphasic in both cell types, but significantly delayed in Purkinje as compared to granule cells. Application of the heavy-metal chelator, TPEN, to Purkinje cells caused a precipitous decline in a proportion of the fura-2 fluorescence signal, indicating that MeHg causes release of Ca2+ and non-Ca2+ divalent cations. Purkinje cells were also more resistant than granule cells to the neurotoxic effects of MeHg. At 24.5 It after-application of 5 mu M MeHg, 97.7% of Purkinje cells were viable. At 3 mu M MeHg there was no detectable loss of Purkinje cell viability. In contrast, only 40.6% of cerebellar granule cells were alive 24.5 h after application of 3 mu M MeHg. In conclusion, Purkinje neurons in primary cultures appear to be more resistant to MeHg induced dysregulation of divalent cation homeostasis and subsequent cell death when compared to cerebellar granule cells. There is a significant component of non-Ca2+ divalent cation released by MeHg in Purkinje neurons. (c) 2005 Elsevier Inc. All rights reserved.