p38-dependent c-Jun degradation contributes to reduced PGE2 production in sodium orthovanadate-treated macrophages.
BMB Rep
; 55(8): 389-394, 2022 Aug.
Article
en En
| MEDLINE
| ID: mdl-35410635
ABSTRACT
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. [BMB Reports 2022; 55(8) 389-394].
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dinoprostona
/
Lipopolisacáridos
Límite:
Animals
Idioma:
En
Revista:
BMB Rep
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2022
Tipo del documento:
Article