Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL pathway
10.3969/j.issn.1000-484X.2025.07.018
- VernacularTitle: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
- Author:
Shujun WANG
1
;
Qiqi LIANG
;
Siyuan CHEN
;
Qingbing ZHA
Author Information
1. 暨南大学附属第一医院胎儿医学科,广州 510630
- Publication Type:Journal Article
- Keywords:
Necroptosis;
Podocytes;
Macrophages;
MPC-5;
Disulfiram
- From:
Chinese Journal of Immunology
2025;41(7):1665-1672
- CountryChina
- Language:Chinese
-
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.
