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Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression
BACKGROUND: Previous studies have revealed that Sirt3 deficiency is associated with several inflammatory responses. The purpose of this study is to investigate the role and potential molecular mechanisms of Sirt3 in the inflammation induced by monosodium urate (MSU) crystals. METHODS: The Sirt3 expr...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354977/ https://www.ncbi.nlm.nih.gov/pubmed/37468929 http://dx.doi.org/10.1186/s13075-023-03107-6 |
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author | Lv, Linxi Jiang, Hui Song, Dianze Zhou, Xiaoqin Chen, Feng Ren, Long Xie, Yongen Zeng, Mei |
author_facet | Lv, Linxi Jiang, Hui Song, Dianze Zhou, Xiaoqin Chen, Feng Ren, Long Xie, Yongen Zeng, Mei |
author_sort | Lv, Linxi |
collection | PubMed |
description | BACKGROUND: Previous studies have revealed that Sirt3 deficiency is associated with several inflammatory responses. The purpose of this study is to investigate the role and potential molecular mechanisms of Sirt3 in the inflammation induced by monosodium urate (MSU) crystals. METHODS: The Sirt3 expression level in the peripheral blood mononuclear cells (PBMCs) of patients with gout was measured. Function and molecular mechanism of Sirt3 in MSU crystal-induced inflammation were investigated in bone marrow-derived macrophages (BMDMs), C57BL/6 mouse, and Sirt3(−/−) mouse. RESULTS: Sirt3 expression was decreased in the PBMCs of patients with gout. Sirt3 agonist (Viniferin) inhibited the acetylation levels of mitochondrial proteins including the SOD2 protein. RNA sequencing, bio-informatics analysis, RT-PCR, and Western blot demonstrated that Sirt3 could suppress the expression of Acod1 (Irg1), which plays an important role in gout. In BMDMs treated with palmitic acid (C16:0) plus MSU crystals, Acod1 knockdown repressed mitochondrial reactive oxygen species (mtROS) over-production, macrophage migration, and mitochondrial fragmentation, and Acod1 improved AMPK activity. The over-expression of Acod1 did not significantly affect the level of itaconic acid, but greatly decreased the levels of some important intermediate metabolites of the tricarboxylic acid (TCA) cycle. These data indicate that Acod1 exerts a pro-inflammatory role in MSU crystal-induced inflammation and is independent of the metabolic level of itaconic acid. Sirt3 deficiency exacerbates inflammatory response induced by MSU crystals in vitro and in vivo. CONCLUSION: The current study has shown that Sirt3 can alleviate the MSU crystal-induced inflammation by inhibiting the expression of Acod1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03107-6. |
format | Online Article Text |
id | pubmed-10354977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103549772023-07-20 Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression Lv, Linxi Jiang, Hui Song, Dianze Zhou, Xiaoqin Chen, Feng Ren, Long Xie, Yongen Zeng, Mei Arthritis Res Ther Research BACKGROUND: Previous studies have revealed that Sirt3 deficiency is associated with several inflammatory responses. The purpose of this study is to investigate the role and potential molecular mechanisms of Sirt3 in the inflammation induced by monosodium urate (MSU) crystals. METHODS: The Sirt3 expression level in the peripheral blood mononuclear cells (PBMCs) of patients with gout was measured. Function and molecular mechanism of Sirt3 in MSU crystal-induced inflammation were investigated in bone marrow-derived macrophages (BMDMs), C57BL/6 mouse, and Sirt3(−/−) mouse. RESULTS: Sirt3 expression was decreased in the PBMCs of patients with gout. Sirt3 agonist (Viniferin) inhibited the acetylation levels of mitochondrial proteins including the SOD2 protein. RNA sequencing, bio-informatics analysis, RT-PCR, and Western blot demonstrated that Sirt3 could suppress the expression of Acod1 (Irg1), which plays an important role in gout. In BMDMs treated with palmitic acid (C16:0) plus MSU crystals, Acod1 knockdown repressed mitochondrial reactive oxygen species (mtROS) over-production, macrophage migration, and mitochondrial fragmentation, and Acod1 improved AMPK activity. The over-expression of Acod1 did not significantly affect the level of itaconic acid, but greatly decreased the levels of some important intermediate metabolites of the tricarboxylic acid (TCA) cycle. These data indicate that Acod1 exerts a pro-inflammatory role in MSU crystal-induced inflammation and is independent of the metabolic level of itaconic acid. Sirt3 deficiency exacerbates inflammatory response induced by MSU crystals in vitro and in vivo. CONCLUSION: The current study has shown that Sirt3 can alleviate the MSU crystal-induced inflammation by inhibiting the expression of Acod1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03107-6. BioMed Central 2023-07-19 2023 /pmc/articles/PMC10354977/ /pubmed/37468929 http://dx.doi.org/10.1186/s13075-023-03107-6 Text en © The Author(s) 2023 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lv, Linxi Jiang, Hui Song, Dianze Zhou, Xiaoqin Chen, Feng Ren, Long Xie, Yongen Zeng, Mei Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression |
title | Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression |
title_full | Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression |
title_fullStr | Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression |
title_full_unstemmed | Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression |
title_short | Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression |
title_sort | sirt3 improves monosodium urate crystal-induced inflammation by suppressing acod1 expression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354977/ https://www.ncbi.nlm.nih.gov/pubmed/37468929 http://dx.doi.org/10.1186/s13075-023-03107-6 |
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