Role of p38 mitogen-activated protein kinase in the 4-hydroxy-2-nonenal-induced cyclooxygenase-2 expression

Takeshi Kumagai, Yoshimasa Nakamura, Toshihiko Osawa, Koji Uchida

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46 Citations (Scopus)


COX-2 is rapidly expressed by various stimuli and plays a key role in conversion of free arachidonic acid to prostaglandins (PGs). 4-Hydroxy-2-nonenal (HNE), one of the lipid peroxidation end-products, has been recently identified as a potent COX-2 inducer in rat epithelial cell RL34 cells (Kumagai et al. (2000) Biochem. Biophys. Res. Commun. 273, 437-441. Here we investigated the molecular mechanism underlying the COX-2 induction by HNE mainly focusing on the activation of p38 mitogen-activated protein kinase (MAPK) pathways. The observations that (i) HNE induced phosphorylation of p38 MAPK and MKK3/MKK6 within 5 min and that (ii) SB203580, a p38 MAPK-specific inhibitor, suppressed the HNE-induced COX-2 expression suggested that the p38 MAPK pathway was involved in the HNE-induced COX-2 expression. Overexpression of p38 MAPK enhanced the HNE-induced COX-2 expression, whereas the overexpression of dominant negative p38 MAPK suppressed it. Furthermore, we also found that HNE upregulated the COX-2 expression by the stabilization of COX-2 mRNA via the p38 MAPK pathway.

Original languageEnglish
Pages (from-to)240-245
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number2
Publication statusPublished - Jan 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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