中国免疫学杂志2025，Vol.41Issue(7)：1665-1672,8.DOI:10.3969/j.issn.1000-484X.2025.07.018
双硫仑通过阻断RIPK1/RIPK3/MLKL通路抑制肾足细胞和巨噬细胞发生坏死性凋亡
Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL pathway
摘要
Abstract
Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.关键词
坏死性凋亡/肾足细胞/巨噬细胞/MPC-5/双硫仑Key words
Necroptosis/Podocytes/Macrophages/MPC-5/Disulfiram分类
医药卫生引用本文复制引用
王淑军,梁琪琦,陈思远,查庆兵..双硫仑通过阻断RIPK1/RIPK3/MLKL通路抑制肾足细胞和巨噬细胞发生坏死性凋亡[J].中国免疫学杂志,2025,41(7):1665-1672,8.基金项目
国家自然科学基金项目(82274167) （82274167）
广州市科技计划项目(202201020083). （202201020083）
