4-Hydroxy-2-nonenal, the end product of lipid peroxidation, is a specific inducer of cyclooxygenase-2 gene expression

Takeshi Kumagai, Yoshiyuki Kawamoto, Yoshimasa Nakamura, Ichiro Hatayama, Kimihiko Satoh, Toshihiko Osawa, Koji Uchida

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)


Cyclooxygenase-2 (COX-2), an enzyme responsible for catalyzing the committed step in prostanoid biosynthesis, is the product of an immediate early gene capable of being upregulated by diverse stimuli. Based on the experimental evidence that oxidative stress is associated with the upregulation of COX-2, we evaluated the effect of the oxidized fatty acid metabolites on COX-2 induction in rat liver epithelial RL34 cells. Among the compounds tested, only 4-hydroxy-2-nonenal (HNE), a highly mutagenic and genotoxic aldehyde generated during oxidative stress, dramatically induced COX-2. Enhanced gene expression of COX-2 by treatment with HNE was evident as a drastic elevation of the mRNA level. We also found that intracellular glutathione status was strictly related to HNE-induced COX-2 expression. These findings suggest the presence of a signaling pathway in the cellular response mediated by locally produced lipid peroxidation products under oxidative stress. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)437-441
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Jul 5 2000
Externally publishedYes


  • 4-Hydroxy-2-nonenal
  • Cyclooxygenase-2
  • Lipid peroxidation
  • Oxidative stress
  • Prostaglandins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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