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KMID : 0624620220550080389
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BMB Reports
2022 Volume.55 No. 8 p.389 ~ p.394
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p38-dependent c-Jun degradation contributes to reduced PGE2 production in sodium orthovanadate-treated macrophages
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Aziz Nur
Kim Eun-Ji
Yang Yanyan
Kim Han-Gyung
Yu Tao
Cho Jae-Youl
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Abstract
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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 E2 (PGE2) 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 PGE2 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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KEYWORD
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c-Jun degradation, Macrophages, p38 MAPK, Sodium orthovanadate, Ubiquitination
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