Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: A study using green fluorescent protein transgenic zebrafish

Tadayuki Tsujita, Li Li, Hitomi Nakajima, Noriko Iwamoto, Yaeko Nakajima-Takagi, Ken Ohashi, Koichi Kawakami, Yoshito Kumagai, Bruce A. Freeman, Masayuki Yamamoto, Makoto Kobayashi

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Nitro-fatty acids are electrophilic fatty acids produced in vivo from nitrogen peroxide that have many physiological activities. We recently demonstrated that nitro-fatty acids activate the Keap1-Nrf2 system, which protects cells from damage owing to electrophilic or oxidative stresses via transactivating an array of cytoprotective genes, although the molecular mechanism how they activate Nrf2 is unclear. A number of chemical compounds with different structures have been reported to activate the Keap1-Nrf2 system, which can be categorized into at least six classes based on their sensing pathways. In this study, we showed that nitro-oleic acid (OA-NO2), one of major nitro-fatty acids, activates Nrf2 in the same manner that of a cyclopentenone prostaglandin 15-deoxy-δ12,14-prostaglandin J2 (15d-PGJ2) using transgenic zebrafish that expresses green fluorescent protein (GFP) in response to Nrf2 activators. In transgenic embryos, GFP was induced in the whole body by treatment with OA-NO2, 15d-PGJ2 or diethylmaleate (DEM), but not with hydrogen peroxide (H2O2), when exogenous Nrf2 and Keap1 were co-overexpressed. Induction by OA-NO2 or 15d-PGJ2 but not DEM was observed, even when a C151S mutation was introduced in Keap1. Our results support the contention that OA-NO2 and 15d-PGJ2 share an analogous cysteine code as electrophiles and also have similar anti-inflammatory roles.

Original languageEnglish
Pages (from-to)46-57
Number of pages12
JournalGenes to Cells
Volume16
Issue number1
DOIs
Publication statusPublished - 2011 Jan

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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