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Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression
Hepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellula...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986781/ https://www.ncbi.nlm.nih.gov/pubmed/35388144 http://dx.doi.org/10.1038/s42003-022-03251-w |
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author | Jin, Yi Tan, Yanjie Zhao, Pengxiang Guo, Yu Chen, Shilin Wu, Jian Ren, Zhuqing |
author_facet | Jin, Yi Tan, Yanjie Zhao, Pengxiang Guo, Yu Chen, Shilin Wu, Jian Ren, Zhuqing |
author_sort | Jin, Yi |
collection | PubMed |
description | Hepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellular antioxidant and detoxificant. GSTM2 was highly up-regulated in hepatic steatosis tissues and high-fat diet (HFD) fed mice. Loss-of-function GSTM2 mouse model demonstrated that GSTM2 protected mice from excess fat accumulation. Mechanistically, GSTM2 interacted with ASK1 and suppressed its phosphorylation and the activation of subsequent downstream p38-JNK signalling. Moreover, GSTM2 overexpression in the liver effectively ameliorated hepatic lipid accumulation. Therefore, we identified GSTM2 as an important negative regulator in progression of hepatic steatosis via both its detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling. This study showed potential therapeutic function of the DME in progression of hepatic steatosis. |
format | Online Article Text |
id | pubmed-8986781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89867812022-04-22 Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression Jin, Yi Tan, Yanjie Zhao, Pengxiang Guo, Yu Chen, Shilin Wu, Jian Ren, Zhuqing Commun Biol Article Hepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellular antioxidant and detoxificant. GSTM2 was highly up-regulated in hepatic steatosis tissues and high-fat diet (HFD) fed mice. Loss-of-function GSTM2 mouse model demonstrated that GSTM2 protected mice from excess fat accumulation. Mechanistically, GSTM2 interacted with ASK1 and suppressed its phosphorylation and the activation of subsequent downstream p38-JNK signalling. Moreover, GSTM2 overexpression in the liver effectively ameliorated hepatic lipid accumulation. Therefore, we identified GSTM2 as an important negative regulator in progression of hepatic steatosis via both its detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling. This study showed potential therapeutic function of the DME in progression of hepatic steatosis. Nature Publishing Group UK 2022-04-06 /pmc/articles/PMC8986781/ /pubmed/35388144 http://dx.doi.org/10.1038/s42003-022-03251-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Jin, Yi Tan, Yanjie Zhao, Pengxiang Guo, Yu Chen, Shilin Wu, Jian Ren, Zhuqing Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression |
title | Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression |
title_full | Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression |
title_fullStr | Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression |
title_full_unstemmed | Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression |
title_short | Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression |
title_sort | glutathione s-transferase mu 2 inhibits hepatic steatosis via ask1 suppression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986781/ https://www.ncbi.nlm.nih.gov/pubmed/35388144 http://dx.doi.org/10.1038/s42003-022-03251-w |
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