Cadmium exacerbates liver injury by remodeling ceramide metabolism: Multiomics and laboratory evidence
SCIENCE OF THE TOTAL ENVIRONMENT(2024)
摘要
Cadmium (Cd) is a toxic heavy metal that primarily targets the liver. Cd exposure disrupts specific lipid metabolic pathways; however, the underlying mechanisms remain unclear. This study aimed to investigate the lipidomic characteristics of rat livers after Cd exposure as well as the potential mechanisms of Cd-induced liver injury. Our analysis of established Cd-exposed rat and cell models showed that Cd exposure resulted in liver lipid deposition and hepatocyte damage. Lipidomic detection, transcriptome sequencing, and experimental analyses revealed that Cd mainly affects the sphingolipid metabolic pathway and that the changes in ceramide metabolism are the most significant. In vitro experiments revealed that the inhibition of ceramide synthetase activity or activation of ceramide decomposing enzymes ameliorated the proapoptotic and pro-oxidative stress effects of Cd, thereby alleviating liver injury. In contrast, the exogenous addition of ceramide aggravated liver injury. In summary, Cd increased ceramide levels by remodeling ceramide synthesis and catabolism, thereby promoting hepatocyte apoptosis and oxidative stress and ultimately aggravating liver injury. Reducing ceramide levels can
更多查看译文
关键词
Cadmium,Liver injury,Lipidomics,Transcriptomics,Ceramide
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要