MARCKS is involved in methylmercury-induced decrease in cell viability and nitric oxide production in EA.hy926 cells.
MARCKS is involved in methylmercury-induced decrease in cell viability and nitric oxide production in EA.hy926 cells.
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DOI：
10.1292/jvms.16-0249
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Miyamoto A
中科院分区：
文献类型：
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作者：
VAN Dao C;Islam MZ;Sudo K;Shiraishi M;Miyamoto A
甲基汞（MeHg）是一种持久性环境污染物，已在世界范围内报告。据报告，接触甲基汞会增加患心血管疾病的风险;然而，甲基汞对心血管系统产生毒性作用的机制尚未得到很好的阐明。我们以前曾报道，小鼠暴露于甲基汞增加血压沿着受损内皮依赖性血管舒张。在这项研究中，我们调查了甲基汞对人内皮细胞系，EA.hy926的毒性作用。此外，我们试图阐明肉豆蔻酰丙氨酸丰富的C激酶底物（MARCKS）在甲基汞的毒性机制在EA.hy926细胞中的作用。细胞暴露于甲基汞（0.1-10 µM）24小时后，细胞活力呈剂量依赖性下降。次最大浓度的甲基汞治疗减少细胞迁移的伤口愈合试验，管形成基质胶和自发的一氧化氮（NO）的EA.hy926细胞。甲基汞暴露还引起MARCKS表达减少和MARCKS磷酸化增加。MARCKS基因敲除或过表达不仅改变了EA.hy926细胞的迁移、微管形成和NO生成等细胞功能，而且还降低了甲基汞诱导的细胞活力和NO生成。这些结果表明MARCKS在内皮细胞功能中发挥了广泛的作用，并且MARCKS参与了甲基汞诱导的毒性。
Methylmercury (MeHg) is a persistent environmental contaminant that has been reported worldwide. MeHg exposure has been reported to lead to increased risk of cardiovascular diseases; however, the mechanisms underlying the toxic effects of MeHg on the cardiovascular system have not been well elucidated. We have previously reported that mice exposed to MeHg had increased blood pressure along with impaired endothelium-dependent vasodilation. In this study, we investigated the toxic effects of MeHg on a human endothelial cell line, EA.hy926. In addition, we have tried to elucidate the role of myristoylated alanine-rich C kinase substrate (MARCKS) in the MeHg toxicity mechanism in EA.hy926 cells. Cells exposed to MeHg (0.1–10 µM) for 24 hr showed decreased cell viability in a dose-dependent manner. Treatment with submaximal concentrations of MeHg decreased cell migration in the wound healing assay, tube formation on Matrigel and spontaneous nitric oxide (NO) production of EA.hy926 cells. MeHg exposure also elicited a decrease in MARCKS expression and an increase in MARCKS phosphorylation. MARCKS knockdown or MARCKS overexpression in EA.hy926 cells altered not only cell functions, such as migration, tube formation and NO production, but also MeHg-induced decrease in cell viability and NO production. These results suggest the broad role played by MARCKS in endothelial cell functions and the involvement of MARCKS in MeHg-induced toxicity.