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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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p38-dependent c-Jun degradation contributes to reduced PGE2 production in sodium orthovanadate-treated macrophages

  • Aziz, Nur (Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Kim, Eunji (Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Yang, Yanyan (Institute for Translational Medicine, School of Basic Medicine, Qingdao University) ;
  • Kim, Han Gyung (Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Yu, Tao (Institute for Translational Medicine and Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University) ;
  • Cho, Jae Youl (Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University)
  • Received : 2021.08.18
  • Accepted : 2022.03.18
  • Published : 2022.08.31
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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.

Keywords

Acknowledgement

This research was funded by the Basic Science Research Program through the National Research Foundation of Korea (NRF), (Grant number: 2017R1A6A1A03015642) and by Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (Grant No.: 2020R1A6C101A191), Korea.

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