Sodium arsenite exposure alters cell migration, focal adhesion localization and decreases tyrosine phosphorylation of focal adhesion kinase in H9C2 myoblasts.
Sodium arsenite exposure alters cell migration, focal adhesion localization and decreases tyrosine phosphorylation of focal adhesion kinase in H9C2 myoblasts.
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亚砷酸钠暴露会改变 H9C2 成肌细胞中的细胞迁移、粘着斑定位并降低粘着斑激酶的酪氨酸磷酸化。
DOI：
10.1093/toxsci/kfi032
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Welsh,MichaelJ
中科院分区：
文献类型：
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作者：
Yancy,ShannonL;Shelden,EricA;Gilmont,RobertR;Welsh,MichaelJ
据报道，暴露于环境毒物砷会产生多种效应，包括信号转导通路的中断、细胞增殖和凋亡。这表明亚砷酸盐可能没有特定的目标，而是具有极其广泛的影响。本研究旨在验证亚砷酸盐改变成肌细胞粘着斑结构和功能信号的假说。将H9C2细胞暴露于1、2.5、5或10 μM亚砷酸钠48 h。MTT代谢和中性红、台盼蓝和碘化丙啶染色表明，5 μM或更低浓度的亚砷酸钠处理没有明显的细胞毒性。在这些剂量下，亚砷酸钠不影响细胞中聚合肌动蛋白的量、蛋白质合成速率或细胞中黏着斑蛋白、talin、桩蛋白和粘着斑激酶（FAK）的量。然而，亚砷酸钠处理的细胞含有较少的局灶性粘连与改变的分布模式。亚砷酸钠暴露引起细胞迁移和细胞附着率的剂量依赖性降低。细胞覆盖的基底的平均面积也减少了，尽管细胞的平均体积没有受到显著影响。亚砷酸钠暴露导致FAK、其底物桩蛋白和FAK自磷酸化位点Tyr397的酪氨酸磷酸化减少。我们的研究结果表明，亚砷酸钠可以改变粘着斑的结构和功能，从而影响细胞的附着和迁移，并可能影响粘着斑功能的其他方面，如整合素信号。这些不同的后果可能介导的FAK酪氨酸磷酸化的相对特异性抑制，修改支架蛋白。
Exposure to the environmental toxicant arsenic is reported to produce a variety of effects including disruption of signal transduction pathways, cell proliferation, and apoptosis. This suggests that arsenite may not have specific targets but rather extremely broad effects. The present study was designed to test the hypothesis that arsenite alters signaling involved in focal adhesion structure and function in cultured myoblasts. H9C2 cells were exposed to 1, 2.5, 5, or 10 μM sodium arsenite for 48 h. MTT metabolism and staining by neutral red, trypan blue, and propidium iodide showed that sodium arsenite treatments of 5 μM or less were not overtly cytotoxic. At these doses, sodium arsenite did not affect the amount of polymerized actin in cells, rate of protein synthesis, or amounts of vinculin, talin, paxillin, and focal adhesion kinase (FAK) in cells. However, sodium arsenite-treated cells contained fewer focal adhesions with an altered distribution pattern. Sodium arsenite exposure caused a dose-dependent reduction in cell migration and cell attachment rates. The average area of substrate covered by a cell was also reduced, although the average volume of cells was not significantly affected. Sodium arsenite exposure resulted in reduced tyrosine phosphorylation of FAK, its substrate paxillin and the FAK auto- phosphorylation site, Tyr397. Our results indicate that sodium arsenite can alter focal adhesion structure and function, thus affecting cell attachment and migration and possibly other aspects of focal adhesion function such as integrin signaling. These diverse consequences may be mediated by a relatively specific inhibition of FAK tyrosine phosphorylation, modifying scaffolding proteins.