Homocysteine Suppresses Autophagy Through AMPK-mTOR-TFEB Signaling in Human THP-1 Macrophages

被引:12
作者
Yang, Yu-ping [1 ]
Ren, Yong-gang [2 ]
Cai, Bi-qing [1 ]
Huang, Dan-dan [1 ]
机构
[1] North Sichuan Med Coll, Sch Basic Med, 234 Fujiang Rd, Nanchong 637007, Sichuan, Peoples R China
[2] North Sichuan Med Coll, Res Ctr Clin Med Sci, Affiliated Hosp, Nanchong, Peoples R China
关键词
homocysteine; THP-1; macrophages; autophagy; AMPK-mTOR-TFEB signaling pathway; CARDIOVASCULAR RISK; ATHEROSCLEROSIS; HYPERHOMOCYSTEINEMIA; DIFFERENTIATION; HOMEOSTASIS; METABOLISM; EXPRESSION; PROTEINS; MONOCYTE; IMMUNITY;
D O I
10.1097/FJC.0000000000001232
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Hyperhomocysteinemia is an independent risk factor for atherosclerosis. It is known that macrophage autophagy plays a protective role in atherosclerosis and that hyperhomocysteinemia is strongly linked to autophagy. Therefore, it is of great significance to study the molecular mechanisms underlying the effect of homocysteine (Hcy) on macrophage autophagy. This study aimed to investigate the effects of Hcy on autophagy in a human acute monocytic leukemia cell line (THP-1). The Hcy-treated THP-1 cells exhibited increased levels of the autophagy substrate SQSTM1 (p62) and decreased levels of the autophagy markers LC3 II/I and Beclin-1, indicating a decrease in autophagy in vitro. Furthermore, Western blotting showed that Hcy significantly increased the levels of p-mTOR and nuclear TFEB and decreased the levels of p-AMPK and cytoplasmic TFEB. These data suggest that Hcy inhibits autophagosome formation in human THP-1 macrophages through the AMPK-mTOR-TFEB signaling pathway. Our findings provide new insights into the mechanisms of atherosclerotic diseases caused by Hcy.
引用
收藏
页码:730 / 738
页数:9
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