苦马豆素
自噬
溶酶体
组织蛋白酶D
细胞生物学
细胞毒性
糖基化
毒性
生物
化学
生物化学
酶
体外
有机化学
细胞凋亡
作者
Shuai Wang,Panpan Tan,Hongwei Wang,Jicang Wang,Cai Zhang,Hao Lu,Baoyu Zhao
标识
DOI:10.1016/j.cbi.2023.110629
摘要
Swainsonine (SW) is the primary toxin in locoweed, a poisonous plant. SW can cause animal poisoning, affect the quality and safety of meat products and threaten human health, but the mechanism of its toxicity is little defined. Here, we identified 159 differentially expressed proteins, many of which are involved in autophagy and glycosylation modification processes, using proteomics sequencing analysis. O-linked-N-acetylglucosamylation (O-GlcNAcylation) is a glycosylation modification widely involved in various biological processes. Our results show that SW toxicity is related to O-GlcNAcylation. In addition, increased O-GlcNAcylation with the O-GlcNAcase (OGA) inhibitor TMG promoted autophagy, while decreased O-GlcNAcylation with the O-GlcNAc transferase (OGT) inhibitor OSMI inhibited autophagy. Further analysis by Immunoprecipitation (IP) showed that SW could change the O-GlcNAcylation of Cathepsin D (CTSD), reducing the expression of mature CTSD (m-CTSD). In summary, these findings suggest that SW inhibits the O-GlcNAcylation of CTSD, affecting its maturation and leading to the impairment of lysosome function. Consequently, it inhibits autophagy degradation, and causes cytotoxicity, providing a new theoretical basis for SW toxicological mechanism.
科研通智能强力驱动
Strongly Powered by AbleSci AI