Inhibition of ROS/NLRP3/Caspase-1 mediated pyroptosis alleviates excess molybdenum-induced apoptosis in duck renal tubular epithelial cells

Ecotoxicology and Environmental Safety

Caiying Zhang¹  Zejing Wei²  Shaoxing Pi²  Chang Wang²  Chenghong Xing²  Guoliang Hu²  Fan Yang²  Gaohui Nie³ 

[1]Corresponding authors.

[2]Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China

[3]School of Information Technology, Jiangxi University of Finance and Economics, Nanchang 330032, Jiangxi, PR China

关键词: Molybdenum;    Pyroptosis;    Apoptosis;    Renal tubular epithelial cell;    Duck;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective: Excess molybdenum (Mo) is harmful to the body, and the kidney is the vital target organ for Mo exposure. This study focused on the impacts of excess Mo on pyroptosis and the relationship between pyroptosis and apoptosis in kidney. Methods: The duck renal tubular epithelial cells were treated with (NH4)6Mo7O24·4H2O (0, 480, 720 and 960 μM Mo), N-acetyl-L-cysteine (NAC) (100 μM), Z-YVAD-fluoromethylketone (YVAD) (10 μM) and the combination of Mo and NAC or YVAD for 12 h. The LDH release and IL-1β, IL-18 contents of cell supernatant were detected by LDH and ELISA kits. The MMP and ROS level were measured using MMP and ROS kits by flow cytometry. The apoptotic rate of cell was detected by AO/EB counterstaining. Pyroptosis and apoptosis-related factors mRNA and protein levels were assayed by real-time qPCR and western blot, respectively. Results: Excessive Mo markedly increased LDH, IL-18, IL-1β releases and induced overproduction of ROS, pyroptosis-related factors mRNA and protein levels. NAC and YVAD dramatically decreased pyroptosis induced by Mo. Simultaneously, YVAD significantly changed apoptosis-related factors mRNA and protein levels, and reduced cell apoptotic rate. Conclusion: Excessive Mo exposure can induce pyroptosis by the ROS/NLRP3/Caspase-1 pathway in duck renal tubular epithelial cells, and restraining pyroptosis of Caspase-1 dependence might weaken excess Mo-induced apoptosis. The study provides theoretical basis for excess Mo exposure nephrotoxic researches on waterfowl and the interplay between pyroptosis and apoptosis highlights a new sight into the mechanism of Mo-induced nephrotoxicity.

【 授权许可】

Unknown