Necroptosis and NLPR3 inflammasome activation mediated by ROS/JNK pathway participate in AlCl3-induced kidney damage

Jiayu Du; Xuliang Zhang; Jian Zhang; Siming Huo; Bo Li; Qi Wang; Miao Song; Bing Shao; Yanfei Li

doi:10.1016/j.fct.2023.113915

Necroptosis and NLPR3 inflammasome activation mediated by ROS/JNK pathway participate in AlCl₃-induced kidney damage

Food Chem Toxicol. 2023 Aug:178:113915. doi: 10.1016/j.fct.2023.113915. Epub 2023 Jun 29.

Authors

Jiayu Du¹, Xuliang Zhang¹, Jian Zhang¹, Siming Huo¹, Bo Li¹, Qi Wang¹, Miao Song¹, Bing Shao¹, Yanfei Li²

Affiliations

¹ Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
² Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address: liyanfei@neau.edu.cn.

PMID: 37393014
DOI: 10.1016/j.fct.2023.113915

Abstract

Aluminum (Al) is a common environmental pollutant that can induce kidney damage. However, the mechanism is not clear. In the present study, to explored the exact mechanism of AlCl₃-induced nephrotoxicity, C57BL/6 N male mice and HK-2 cells were used as experimental subjects. Our results showed that Al induced reactive oxygen species (ROS) overproduction, c-Jun N-terminal kinase (JNK) signaling activation, RIPK3-dependent necroptosis, NLRP3 inflammasome activation, and kidney damage. In addition, inhibiting JNK signaling could downregulate the protein expressions of necroptosis and NLRP3 inflammasome, thereby alleviating kidney damage. Meanwhile, clearing ROS effectively inhibited JNK signaling activation, which in turn inhibited necroptosis and NLRP3 inflammasome activation, ultimately alleviating kidney damage. In conclusion, these findings suggest that necroptosis and NLPR3 inflammasome activation mediated by ROS/JNK pathway participate in AlCl₃-induced kidney damage.

Keywords: Aluminum; Kidney damage; NLRP3 inflammasome; Necroptosis; ROS/JNK pathway.

MeSH terms

Animals
Inflammasomes*
Kidney / metabolism
MAP Kinase Signaling System*
Male
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Necroptosis
Reactive Oxygen Species / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Reactive Oxygen Species