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

Yang, Anning ; Zeng, Wen ; Zhang, Hongwen ; Hao, Yinju ; Wang, Qingqing ; Sun, Yue ; Quan, Shangkun ; Ding, Ning ; Yang, Xiaoling and Sun, Jianmin LU , et al. (2023) In Acta Biochimica et Biophysica Sinica 55(8). p.1184-1192
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autophagy, DNA methylation, DNA methyltransferase 3b, homocysteine, TFEB
in
Acta Biochimica et Biophysica Sinica
volume
55
issue
8
pages
9 pages
publisher
Oxford University Press
external identifiers
  • pmid:37021975
  • scopus:85168777744
ISSN
1672-9145
DOI
10.3724/abbs.2023060
language
English
LU publication?
yes
id
9131bd3d-afc9-45d3-a988-41797c34ae14
date added to LUP
2023-11-06 10:05:28
date last changed
2024-04-19 03:37:12
@article{9131bd3d-afc9-45d3-a988-41797c34ae14,
  abstract     = {{<p>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.</p>}},
  author       = {{Yang, Anning and Zeng, Wen and Zhang, Hongwen and Hao, Yinju and Wang, Qingqing and Sun, Yue and Quan, Shangkun and Ding, Ning and Yang, Xiaoling and Sun, Jianmin and Zhang, Huiping and Liu, Bin and Jiao, Yun and Wu, Kai and Jiang, Yideng}},
  issn         = {{1672-9145}},
  keywords     = {{autophagy; DNA methylation; DNA methyltransferase 3b; homocysteine; TFEB}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1184--1192}},
  publisher    = {{Oxford University Press}},
  series       = {{Acta Biochimica et Biophysica Sinica}},
  title        = {{Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation}},
  url          = {{http://dx.doi.org/10.3724/abbs.2023060}},
  doi          = {{10.3724/abbs.2023060}},
  volume       = {{55}},
  year         = {{2023}},
}