Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation

Autophagy plays a critical role in the physiology and pathophysiology of hepatocytes. High level of homocysteine (Hcy) promotes autophagy in hepatocytes, but the underlying mechanism is still unknown. Here, we investigate the relationship between Hcy-induced autophagy level and the expression of nuclear transcription factor EB (TFEB). The results show that Hcy-induced autophagy level is mediated by upregulation of TFEB. Silencing of TFEB decreases the level of autophagy-related protein LC3BII/I and increases p62 expression level in hepatocytes after exposure to Hcy. Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of the TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). In summary, this study shows that Hcy can activate autophagy by inhibiting DNMT3b-mediated DNA methylation and upregulating TFEB expression. These findings provide another new mechanism for Hcy-induced autophagy in hepatocytes.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:55

Enthalten in:

Acta biochimica et biophysica Sinica - 55(2023), 8 vom: 06. Apr., Seite 1184-1192

Sprache:

Englisch

Beteiligte Personen:

Yang, Anning [VerfasserIn]
Zeng, Wen [VerfasserIn]
Zhang, Hongwen [VerfasserIn]
Hao, Yinju [VerfasserIn]
Wang, Qingqing [VerfasserIn]
Sun, Yue [VerfasserIn]
Quan, Shangkun [VerfasserIn]
Ding, Ning [VerfasserIn]
Yang, Xiaoling [VerfasserIn]
Sun, Jianmin [VerfasserIn]
Zhang, Huiping [VerfasserIn]
Liu, Bin [VerfasserIn]
Jiao, Yun [VerfasserIn]
Wu, Kai [VerfasserIn]
Jiang, Yideng [VerfasserIn]

Links:

Volltext

Themen:

0LVT1QZ0BA
9007-49-2
Autophagy
DNA
DNA methylation
DNA methyltransferase 3b
Homocysteine
Journal Article
TFEB

Anmerkungen:

Date Completed 29.08.2023

Date Revised 13.12.2023

published: Print

Citation Status MEDLINE

doi:

10.3724/abbs.2023060

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM355266709