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Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site
Pyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801742/ https://www.ncbi.nlm.nih.gov/pubmed/33431796 http://dx.doi.org/10.1038/s41419-020-03317-9 |
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author | Wang, Yao Chen, Qian Jiao, Fangzhou Shi, Chunxia Pei, Maohua Wang, Luwen Gong, Zuojiong |
author_facet | Wang, Yao Chen, Qian Jiao, Fangzhou Shi, Chunxia Pei, Maohua Wang, Luwen Gong, Zuojiong |
author_sort | Wang, Yao |
collection | PubMed |
description | Pyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of HDAC2 could reduce the level of pyroptosis in ALF through ULK1-NLRP3-pyroptosis pathway. The role of HDAC2 on ULK1-NLRP3-pyroptosis pathway during ALF was detected in clinical samples. The mechanism was investigated in transfected cells or in ALF mouse model. The RNA-sequencing results revealed that ULK1 was a negative target regulatory molecule by HDAC2. During the process of pyroptosis, the HDAC2 exerted the antagonistic effect with ULK1 by the K68 acetylation site in L02 cells. Then the role of HDAC2 on ULK1-NLRP3-pyroptosis pathway in ALF mouse model was also detected. Moreover, the related molecules to ULK1-NLRP3-pyroptosis pathway were verified different expression in normal health donors and clinical ALF patients. HDAC2 in hepatocytes plays a pivotal role in an ULK1-NLRP3 pathway driven auto-amplification of pyroptosis in ALF. One of the important mechanisms is that inhibition HDAC2 to reduce pyroptosis may be by modulating the K68 lysine site of ULK1. |
format | Online Article Text |
id | pubmed-7801742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78017422021-01-21 Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site Wang, Yao Chen, Qian Jiao, Fangzhou Shi, Chunxia Pei, Maohua Wang, Luwen Gong, Zuojiong Cell Death Dis Article Pyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of HDAC2 could reduce the level of pyroptosis in ALF through ULK1-NLRP3-pyroptosis pathway. The role of HDAC2 on ULK1-NLRP3-pyroptosis pathway during ALF was detected in clinical samples. The mechanism was investigated in transfected cells or in ALF mouse model. The RNA-sequencing results revealed that ULK1 was a negative target regulatory molecule by HDAC2. During the process of pyroptosis, the HDAC2 exerted the antagonistic effect with ULK1 by the K68 acetylation site in L02 cells. Then the role of HDAC2 on ULK1-NLRP3-pyroptosis pathway in ALF mouse model was also detected. Moreover, the related molecules to ULK1-NLRP3-pyroptosis pathway were verified different expression in normal health donors and clinical ALF patients. HDAC2 in hepatocytes plays a pivotal role in an ULK1-NLRP3 pathway driven auto-amplification of pyroptosis in ALF. One of the important mechanisms is that inhibition HDAC2 to reduce pyroptosis may be by modulating the K68 lysine site of ULK1. Nature Publishing Group UK 2021-01-11 /pmc/articles/PMC7801742/ /pubmed/33431796 http://dx.doi.org/10.1038/s41419-020-03317-9 Text en © The Author(s) 2021 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/. |
spellingShingle | Article Wang, Yao Chen, Qian Jiao, Fangzhou Shi, Chunxia Pei, Maohua Wang, Luwen Gong, Zuojiong Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site |
title | Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site |
title_full | Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site |
title_fullStr | Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site |
title_full_unstemmed | Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site |
title_short | Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site |
title_sort | histone deacetylase 2 regulates ulk1 mediated pyroptosis during acute liver failure by the k68 acetylation site |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801742/ https://www.ncbi.nlm.nih.gov/pubmed/33431796 http://dx.doi.org/10.1038/s41419-020-03317-9 |
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