Increased expression of TCF3, transcription factor 3, is a defense response against methylmercury toxicity in mouse neuronal C17.2 cells
Increased expression of TCF3, transcription factor 3, is a defense response against methylmercury toxicity in mouse neuronal C17.2 cells
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TCF3（转录因子 3）表达增加是小鼠神经元 C17.2 细胞针对甲基汞毒性的防御反应
DOI：
10.1007/s43188-021-00087-0
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发表时间：
2021
影响因子：
2.3
通讯作者：
Hwang Gi-Wook
中科院分区：
文献类型：
--
作者：
Toyama Takashi;Wang Yanjiao;Kim Min-Seok;Takahashi Tsutomu;Naganuma Akira;Hwang Gi-Wook
甲基汞是一种环境污染物，可引起强烈的神经毒性。我们以前确定转录因子3（TCF 3）作为一种转录因子，在用甲基汞处理的小鼠的大脑中被激活，并报告说，甲基汞的敏感性增加的细胞中，TCF 3的表达被抑制。然而，甲基汞激活TCF 3和TCF 3降低甲基汞毒性的机制仍不清楚。我们发现，用甲基汞处理小鼠神经元C17.2细胞增加了TCF 3蛋白水平，并促进了TCF 3与DNA共有序列的结合。在用转录抑制剂放线菌素D处理的细胞中，在甲基汞暴露下也观察到TCF 3蛋白水平的增加。然而，在放线菌酮，翻译抑制剂的存在下，甲基汞延迟TCF 3蛋白的降解。此外，用蛋白酶体抑制剂MG 132处理，增加了TCF 3蛋白水平，并且在这些条件下甲基汞没有显著增加TCF 3蛋白水平。这些结果表明，甲基汞可能通过抑制蛋白酶体降解TCF 3来增加TCF 3的水平，从而激活TCF 3。以前曾报道，神经元凋亡的诱导参与了甲基汞诱导的脑神经元损伤。虽然细胞凋亡诱导C17.2细胞用甲基汞处理，这种诱导在很大程度上抑制TCF 3的过表达。这些结果表明，TCF 3，这是增加在大脑中接触甲基汞，可能是一种新的防御因子对甲基汞诱导的神经毒性。
Methylmercury is an environmental pollutant that induces potent neurotoxicity. We previously identified transcription factor 3 (TCF3) as a transcription factor that is activated in the brains of mice treated with methylmercury, and reported that methylmercury sensitivity was increased in cells in which TCF3 expression was suppressed. However, the mechanisms involved in the activation of TCF3 by methylmercury and in the reduction of methylmercury toxicity by TCF3 remained unclear. We found that treatment of mouse neuronal C17.2 cells with methylmercury increased TCF3 protein levels and promoted the binding of TCF3 to DNA consensus sequences. In cells treated with actinomycin D, a transcription inhibitor, an increase in TCF3 protein levels was also observed under methylmercury exposure. However, in the presence of cycloheximide, a translation inhibitor, methylmercury delayed the degradation of TCF3 protein. In addition, treatment with MG132, a proteasome inhibitor, increased TCF3 protein levels, and there was not significant increase in TCF3 protein levels by methylmercury under these conditions. These results suggest that methylmercury may activate TCF3 by increasing its levels through inhibition of TCF3 degradation by the proteasome. It has been previously reported that the induction of apoptosis in neurons is involved in methylmercury-induced neuronal damage in the brain. Although apoptosis was induced in C17.2 cells treated with methylmercury, this induction was largely suppressed by overexpression of TCF3. These results indicate that TCF3, which is increased in the brain upon exposure to methylmercury, may be a novel defense factor against methylmercury-induced neurotoxicity.