中国动脉硬化杂志2025，Vol.33Issue(6)：474-480,7.DOI:10.20039/j.cnki.1007-3949.2025.06.003
二甲双胍通过抑制泛素-蛋白酶体系统上调ABCA1表达
Metformin upregulates ABCA1 expression via inhibiting ubiquitin-proteasome system
摘要
Abstract
Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.关键词
二甲双胍/ATP结合盒转运体A1/AMP活化蛋白激酶/MIB E3泛素蛋白连接酶1/蛋白质组学Key words
metformin/ATP-binding cassette transport A1/AMP-activated protein kinase/MIB E3 ubiquitin-protein ligase 1/proteomics分类
医药卫生引用本文复制引用
刘云霞,胡玉霞,高峰,杨艳,范蕾,王敏杰,于凌泽,白图雅,张梦迪,吕晓丽,李君..二甲双胍通过抑制泛素-蛋白酶体系统上调ABCA1表达[J].中国动脉硬化杂志,2025,33(6):474-480,7.基金项目
国家自然科学基金项目(82260709) （82260709）
内蒙古自治区自然科学基金项目(2020BS08010) （2020BS08010）
高校青年科技英才项目(NJYT24069) （NJYT24069）
内蒙古医科大学校级项目(YKD2022MS025) （YKD2022MS025）
