Homocysteine Suppresses Autophagy Through AMPK-mTOR-TFEB Signaling in Human THP-1 Macrophages.
J Cardiovasc Pharmacol
; 79(5): 730-738, 2022 05 01.
Article
en En
| MEDLINE
| ID: mdl-35121714
ABSTRACT
ABSTRACT 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Hiperhomocisteinemia
/
Aterosclerosis
Tipo de estudio:
Risk_factors_studies
Límite:
Child
/
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article