Alteration in MARCKS phosphorylation and expression by methylmercury in SH-SY5Y cells and rat brain.-猫眼课题宝

甲基汞在 SH-SY5Y 细胞和大鼠脑中改变 MARCKS 磷酸化和表达。

DOI：

10.1016/j.etap.2014.04.025

发表时间：

2014

期刊：

Environmental toxicology and pharmacology

影响因子：

4.3

通讯作者：

中科院分区：

环境科学与生态学3区

文献类型：

作者：

M. Shiraishi;Makoto Hangai;Megumi Yamamoto;M. Sasaki;Atsuhiro Tanabe;Y. Sasaki;A. Miyamoto

介导甲基汞（MeHg）诱导的神经毒性的分子机制尚未完全了解。由于富含豆蔻酰丙氨酸的C激酶底物（MARCKS）在神经细胞的分化和发育中起着重要作用，我们研究了甲基汞诱导的神经母细胞瘤SH-SY 5 Y细胞和大鼠脑中MARCKS表达和磷酸化的变化。暴露于甲基汞诱导SH-SY 5 Y细胞的细胞活力下降，这是伴随着磷酸化的显着增加和MARCKS表达减少。用蛋白激酶C抑制剂或细胞外Ca 2+螯合剂预处理细胞抑制甲基汞诱导的MARCKS磷酸化。在MARCKS敲除细胞中，与对照siRNA相比，甲基汞诱导的细胞死亡显著增加。在脑组织从甲基汞处理的大鼠，MARCKS磷酸化增强嗅球相比，对照组大鼠。本研究可能表明，MARCKS表达或磷酸化的改变对甲基汞诱导的神经毒性有影响。

The molecular mechanisms mediating methylmercury (MeHg)-induced neurotoxicity are not completely understood. Because myristoylated alanine-rich C kinase substrate (MARCKS) plays an essential role in the differentiation and development of neuronal cells, we studied the alteration of MARCKS expression and phosphorylation in MeHg-induced neurotoxicity of neuroblastoma SH-SY5Y cells and in the rat brain. Exposure to MeHg induced a decrease in cell viability of SH-SY5Y cells, which was accompanied by a significant increase in phosphorylation and a reduction in MARCKS expression. Pretreatment of cells with a protein kinase C inhibitor or an extracellular Ca2+chelator suppressed MeHg-induced MARCKS phosphorylation. In MARCKS knock-down cells, MeHg-induced cell death was significantly augmented in comparison to control siRNA. In brain tissue from MeHg-treated rats, MARCKS phosphorylation was enhanced in the olfactory bulb in comparison to control rats. The present study may indicate that alteration in MARCKS expression or phosphorylation has consequences for MeHg-induced neurotoxicity.