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p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages

In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which...

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Autores principales: Aziz, Nur, Kim, Eunji, Yang, Yanyan, Kim, Han Gyung, Yu, Tao, Cho, Jae Youl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442349/
https://www.ncbi.nlm.nih.gov/pubmed/35410635
http://dx.doi.org/10.5483/BMBRep.2022.55.8.115
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author Aziz, Nur
Kim, Eunji
Yang, Yanyan
Kim, Han Gyung
Yu, Tao
Cho, Jae Youl
author_facet Aziz, Nur
Kim, Eunji
Yang, Yanyan
Kim, Han Gyung
Yu, Tao
Cho, Jae Youl
author_sort Aziz, Nur
collection PubMed
description In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which regulate c-Jun degradation within the inflammatory response. Through our study, we found that SO suppressed the production of prostaglandin E(2) (PGE(2)) and the expression of COX-2 in LPS-stimulated RAW264.7 cells. Additionally, SO decreased total c-Jun levels, without altering the amount of mRNA, although the phospho-levels of p38, ERK, and JNK were strongly enhanced. Through the usage of selective MAPK inhibitors, and knockdown and overexpression strategies, p38 was revealed to be a major MAPK which regulates c-Jun degradation. Further analysis indicates that the phosphorylation of p38 is a determinant for c-Jun degradation, and is sufficient to induce ubiquitination-dependent c-Jun degradation, recovered through MG132 treatment. Therefore, our results suggest that the hyperphosphorylation of p38 by SO contributes to c-Jun degradation, which is linked to the suppression of PGE(2) secretion in inflammatory responses; and thus, finding drugs to increase p38 activity could be a novel strategy for the development of anti-inflammatory drugs.
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spelling pubmed-94423492022-09-12 p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages Aziz, Nur Kim, Eunji Yang, Yanyan Kim, Han Gyung Yu, Tao Cho, Jae Youl BMB Rep Article In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which regulate c-Jun degradation within the inflammatory response. Through our study, we found that SO suppressed the production of prostaglandin E(2) (PGE(2)) and the expression of COX-2 in LPS-stimulated RAW264.7 cells. Additionally, SO decreased total c-Jun levels, without altering the amount of mRNA, although the phospho-levels of p38, ERK, and JNK were strongly enhanced. Through the usage of selective MAPK inhibitors, and knockdown and overexpression strategies, p38 was revealed to be a major MAPK which regulates c-Jun degradation. Further analysis indicates that the phosphorylation of p38 is a determinant for c-Jun degradation, and is sufficient to induce ubiquitination-dependent c-Jun degradation, recovered through MG132 treatment. Therefore, our results suggest that the hyperphosphorylation of p38 by SO contributes to c-Jun degradation, which is linked to the suppression of PGE(2) secretion in inflammatory responses; and thus, finding drugs to increase p38 activity could be a novel strategy for the development of anti-inflammatory drugs. Korean Society for Biochemistry and Molecular Biology 2022-08-31 2022-08-31 /pmc/articles/PMC9442349/ /pubmed/35410635 http://dx.doi.org/10.5483/BMBRep.2022.55.8.115 Text en Copyright © 2022 by the The Korean Society for Biochemistry and Molecular Biology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Aziz, Nur
Kim, Eunji
Yang, Yanyan
Kim, Han Gyung
Yu, Tao
Cho, Jae Youl
p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages
title p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages
title_full p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages
title_fullStr p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages
title_full_unstemmed p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages
title_short p38-dependent c-Jun degradation contributes to reduced PGE(2) production in sodium orthovanadate-treated macrophages
title_sort p38-dependent c-jun degradation contributes to reduced pge(2) production in sodium orthovanadate-treated macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442349/
https://www.ncbi.nlm.nih.gov/pubmed/35410635
http://dx.doi.org/10.5483/BMBRep.2022.55.8.115
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