ZFIN ID: ZDB-PUB-101222-1
Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic zebrafish
Tsujita, T., Li, L., Nakajima, H., Iwamoto, N., Nakajima-Takagi, Y., Ohashi, K., Kawakami, K., Kumagai, Y., Freeman, B.A., Yamamoto, M., and Kobayashi, M.
Date: 2011
Source: Genes to cells : devoted to molecular & cellular mechanisms   16(1): 46-57 (Journal)
Registered Authors: Kawakami, Koichi, Kobayashi, Makoto, Li, Li, Nakajima, Hitomi, Nakajima-Takagi, Yaeko, Ohashi, Ken, Tsujita, Tadayuki, Yamamoto, Masayuki
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins/metabolism*
  • Cell Line
  • Cells, Cultured
  • Cyclopentanes
  • Cysteine/genetics
  • Cysteine/metabolism
  • Fatty Acids
  • Green Fluorescent Proteins/metabolism*
  • Hydrogen Peroxide/pharmacology
  • NF-E2-Related Factor 2/genetics
  • NF-E2-Related Factor 2/metabolism*
  • Oleic Acids/pharmacology*
  • Oxidative Stress
  • Prostaglandin D2/analogs & derivatives*
  • Prostaglandin D2/metabolism
  • Prostaglandin D2/pharmacology
  • Prostaglandins/metabolism*
  • Trans-Activators/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed: 21143560 Full text @ Genes Cells
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-NO(2) ), one of major nitro-fatty acids, activates Nrf2 in the same manner that of a cyclopentenone prostaglandin 15-deoxy-Δ(12,14) -prostaglandin J(2) (15d-PGJ(2) ) 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-NO(2) , 15d-PGJ(2) or diethylmaleate (DEM), but not with hydrogen peroxide (H(2) O(2) ), when exogenous Nrf2 and Keap1 were co-overexpressed. Induction by OA-NO(2) or 15d-PGJ(2) but not DEM was observed, even when a C151S mutation was introduced in Keap1. Our results support the contention that OA-NO(2) and 15d-PGJ(2) share an analogous cysteine code as electrophiles and also have similar anti-inflammatory roles.