PUBLICATION
Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic zebrafish
- Authors
- 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.
- ID
- ZDB-PUB-101222-1
- 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
Citation
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. (2011) Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic zebrafish. Genes to cells : devoted to molecular & cellular mechanisms. 16(1):46-57.
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-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping