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 nuc...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2023-04-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023060 |
| _version_ | 1797635862135046144 |
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| author | Yang Anning Zeng Wen Zhang Hongwen Hao Yinju Wang Qingqing Sun Yue Quan Shangkun Ding Ning Yang Xiaoling Sun Jianmin Zhang Huiping Liu Bin Jiao Yun Wu Kai Jiang Yideng |
| author_facet | Yang Anning Zeng Wen Zhang Hongwen Hao Yinju Wang Qingqing Sun Yue Quan Shangkun Ding Ning Yang Xiaoling Sun Jianmin Zhang Huiping Liu Bin Jiao Yun Wu Kai Jiang Yideng |
| author_sort | Yang Anning |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:26:17Z |
| format | Article |
| id | doaj.art-0613d2922f7e4877a23fadc8f74ad33d |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:26:17Z |
| publishDate | 2023-04-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-0613d2922f7e4877a23fadc8f74ad33d2023-11-06T08:34:41ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-04-01551184119210.3724/abbs.202306020d259ccHomocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylationYang Anning0Zeng Wen1Zhang Hongwen2Hao Yinju3Wang Qingqing4Sun Yue5Quan Shangkun6Ding Ning7Yang Xiaoling8Sun Jianmin9Zhang Huiping10Liu Bin11Jiao Yun12Wu Kai13Jiang Yideng14["College of Biology, Hunan University, Changsha, 41000, China","General Hospital of Ningxia Medical University, Yinchuan 750004, China","of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["Department of Scientific Research and Teaching, Central Hospital of Shaoyang, Shaoyang 422000, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["General Hospital of Ningxia Medical University, Yinchuan 750004, China","School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China","Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden"]["Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, China"]["College of Biology, Hunan University, Changsha, 41000, China","of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China"]["General Hospital of Ningxia Medical University, Yinchuan 750004, China"]["of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]["General Hospital of Ningxia Medical University, Yinchuan 750004, China","of Pathophysiology, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China","Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, China"]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. https://www.sciengine.com/doi/10.3724/abbs.2023060homocysteineTFEBautophagyDNA methylationDNA methyltransferase 3b |
| spellingShingle | Yang Anning Zeng Wen Zhang Hongwen Hao Yinju Wang Qingqing Sun Yue Quan Shangkun Ding Ning Yang Xiaoling Sun Jianmin Zhang Huiping Liu Bin Jiao Yun Wu Kai Jiang Yideng Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation Acta Biochimica et Biophysica Sinica homocysteine TFEB autophagy DNA methylation DNA methyltransferase 3b |
| title | Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation |
| title_full | Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation |
| title_fullStr | Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation |
| title_full_unstemmed | Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation |
| title_short | Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation |
| title_sort | homocysteine accelerates hepatocyte autophagy by upregulating tfeb via dnmt3b mediated dna hypomethylation |
| topic | homocysteine TFEB autophagy DNA methylation DNA methyltransferase 3b |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023060 |
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