Inhibition of Autophagy Alleviates Cadmium-Induced Mouse Spleen and Human B Cells Apoptosis. (15th April 2019)

• Record Type: Journal Article
• Authors: Gu, Jie; Wang, Yanwei; Liu, Yanmin; Shi, Meilin; Yin, Liangdong; Hou, Yongzhong; Zhou, Yang; Chu Wong, Chris Kong; Chen, Dongfeng; Guo, Zhigang; Shi, Haifeng
• Is Part Of: Toxicological sciences. Volume 170:Number 1(2019)
• Page Start: 109
• Page End: 122
• Publication Date: 2019-04-15
• Subjects: cadmium -- immunotoxicity -- apoptosis -- VMP1 -- autophagy; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfz089
• Languages: English
• ISSNs: 1096-6080

Abstract

Abstract: Cadmium (Cd) is a toxic heavy metal that can accumulate and cause severe damage to many organs, such as liver, kidney, lung, etc. Cd also significantly suppresses immunity, however, the underlying mechanism involved in Cd-induced immunnotoxicity is still unclear. The present study indicated that semichronic Cd exposure (7 days) induced apoptotic damage of mouse spleen. In human Ramos B cells, Cd exposure also induced apoptosis, which was dependent on Cd-induced vacuole membrane protein 1 (VMP1) expression and autophagy. Cd-induced autophagy and apoptosis were abated when VMP1 expression was knockdown. In addition, Cd-induced VMP1 expression, autophagy, and apoptosis were dependent on the elevation of Ca 2+ and reactive oxygen species (ROS). More important, Cd exposure also induced VMP1 expression and autophagy in mouse spleen tissue, and the intraperitoneal injection of the autophagy inhibitor chloroquine (CQ) into mice effectively reduced Cd-induced spleen apoptotic damage. Taken together, these results indicate Cd-induced autophagy, promotes apoptosis in immune cells, and inhibition of autophagy can alleviate Cd-induced spleen and immune cell apoptosis. This study might provide the groundwork for future studies on Cd-induced immunomodulatory effects and immune diseases.