Aluminum Induced Necroptosis of PC12 Cells via TNFR1-RIP1/RIP3 Signalling Pathway.
Aluminum Induced Necroptosis of PC12 Cells via TNFR1-RIP1/RIP3 Signalling Pathway.
复制标题
铝通过 TNFR1-RIP1/RIP3 信号通路诱导 PC12 细胞坏死性凋亡。
DOI：
10.1007/s11064-022-03653-6
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Qiao Niu
中科院分区：
文献类型：
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作者：
Yue Zhou;Qin Feng;Yaqin Li;Qun Liu;Xiaoyan Zhao;Chunmei Duan;Jingsi Zhang;Qiao Niu
除细胞凋亡外，铝还可引起神经细胞的坏死性下垂，这是最近发现的一种新的程序性坏死，但其分子机制尚未阐明。为了探索这个问题的答案，在本研究中，我们采用了这样的方法，即用麦芽酚铝[200μM siRNA作为干扰技术，探讨肿瘤坏死因子受体1、受体相互作用蛋白1和受体相互作用蛋白3在Al(Mal)3所致的坏死性下垂中的作用。上调磷酸化的混合谱系激酶结构域样蛋白(MLKL)的蛋白表达。此外，在经Al(Mal)3处理的PC12细胞中，发现抑制TNFR1可促进细胞凋亡，抑制RIP1/RIP3和磷酸化MLKL的表达。最后，RIP1/RIP3的缺失减轻了坏死性下垂的程度。简而言之，我们的结果证实了TNFR1-RIP1/RIP3通路可能参与了Al(Mal)3诱导的坏死性下垂。
In addition to apoptosis, it has also been reported that aluminum (Al) causes necroptosis, a new form of programmed necrosis, which has recently been discovered, in nerve cells, but its molecular mechanism is not elucidated. In order to explore the answer, in this study, we apply for this method that after PC12 cells were exposed to maltol aluminum [200 μM siRNA were used as interference technique to explore the role of Tumour necrosis factor receptor 1 (TNFR1), receptor interaction proteins 1 (RIP1) and receptor interaction proteins 3 (RIP3) in necroptosis caused by Al(mal)3. After the end of this research, we demonstrated that, initially, Al(mal)3 could trigger apoptosis and necroptosis in PC12 cells and up-regulate both mRNA and protein expressions of TNFR1, RIP1 and RIP3, also, up-regulate the phosphorylated mixed lineage kinase domain-like protein (MLKL) protein expression. Additionally, in PC12 cells treated with Al(mal)3, suppression of TNFR1 was found to enhance apoptosis and attenuate the expression of RIP1/RIP3 and phosphorylated MLKL. At last, deficiency of RIP1/RIP3 reduced the extent of necroptosis. Briefly, our results verify that the TNFR1-RIP1/RIP3 pathway could be involved in Al(mal)3 induced necroptosis.