Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China.
Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, China.
Neurochem Res. 2022 Oct;47(10):3037-3050. doi: 10.1007/s11064-022-03653-6. Epub 2022 Jul 7.
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 Al(mal)], 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). After the end of this research, we demonstrated that, initially, Al(mal) 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), 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) induced necroptosis.
除了细胞凋亡外，还有研究报道铝（Al）可引起坏死性凋亡，这是一种新发现的程序性细胞坏死形式，最近在神经细胞中被发现，但它的分子机制尚未阐明。为了探索答案，在本研究中，我们采用了这种方法，即在 PC12 细胞暴露于麦芽酚铝[200 μM Al（mal）]后，使用 siRNA 作为干扰技术，探讨肿瘤坏死因子受体 1（TNFR1）、受体相互作用蛋白 1（RIP1）和受体相互作用蛋白 3（RIP3）在 Al（mal）引起的坏死性凋亡中的作用。研究结束后，我们证实，最初，Al（mal）可在 PC12 细胞中引发细胞凋亡和坏死性凋亡，并上调 TNFR1、RIP1 和 RIP3 的 mRNA 和蛋白表达，同时上调磷酸化混合谱系激酶结构域样蛋白（MLKL）的蛋白表达。此外，在 Al（mal）处理的 PC12 细胞中，抑制 TNFR1 可增强细胞凋亡，并减弱 RIP1/RIP3 和磷酸化 MLKL 的表达。最后，RIP1/RIP3 的缺乏减少了坏死性凋亡的程度。简而言之，我们的结果证实，TNFR1-RIP1/RIP3 途径可能参与 Al（mal）诱导的坏死性凋亡。
