p38 and ERK, but not INK, are involved in copper-induced apoptosis in cultured cerebellar granule neurons
p38 and ERK, but not INK, are involved in copper-induced apoptosis in cultured cerebellar granule neurons
复制标题
p38 和 ERK（但不包括 JNK）参与培养的小脑颗粒神经元中铜诱导的细胞凋亡。
DOI：
10.1016/j.bbrc.2008.12.177
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发表时间：
2009-02-20
影响因子：
3.1
通讯作者：
Pi, Rongbiao
中科院分区：
文献类型：
--
作者：
Chen, Xiaohong;Lan, Xiujian;Pi, Rongbiao
铜（Cu 2+）是多种细胞功能的必需元素;然而，它在过量时参与神经毒性事件。Cu 2+诱导的神经毒性机制尚未完全了解。本文研究了Cu ~（2+）对体外培养的小脑颗粒神经元（cCGNs）的毒性作用。用CuCl 2（50和75 μ M）处理cCGNs引起具有凋亡特征的浓度和时间依赖性细胞死亡，包括染色质浓缩和DNA梯状条带。Cu ~（2+）可诱导细胞内活性氧自由基（ROS）的产生，并使细胞内钙离子浓度迅速而轻微地升高。Western blot结果显示，Cu ~（2+）可使p38丝裂原活化蛋白激酶（MAPK）和ERK 1/2的磷酸化水平升高，但对JNK-1的磷酸化水平无明显影响。药理学抑制钙内流、p38 MAPK和ERK 1/2可减轻cCGNs中Cu 2+的毒性。这些结果表明，p38 MAPK和ERK 1/2，而不是JNK，参与铜诱导的cCGNs的凋亡，p38和ERK可能是ROS和钙信号的下游效应器。(C)2009 Elsevier Inc. All rights reserved.
Copper (Cu2+) is an essential element for a variety of cellular functions; however, it is involved in neurotoxic events at excessive doses. Mechanisms of Cu2+-induced neurotoxicity are not well understood. Here, we studied the toxic effects of Cu2+ on cultured cerebellar granule neurons (cCGNs). Treatment of cCGNs with CuCl2 (50 and 75 mu M) caused a concentration- and time-dependent cell death with apoptotic characters, including chromatin condensation and DNA ladder. Cu2+ potently induced reactive oxygen species (ROS), and quickly and slightly increased the intracellular concentration of calcium. Western blot assay showed that Cu2+ increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and ERK1/2, but not that of JNK-1. Pharmacological inhibition of calcium influx, p38 MAPK and ERK1/2 attenuated the Cu2+ toxicity in cCGNs. These findings demonstrate that p38 MAPK and ERK1/2, but not JNK, are involved in apoptosis of cCGNs induced by copper, and p38 and ERK may be the downstream effectors of ROS and calcium signaling. (C) 2009 Elsevier Inc. All rights reserved.