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

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?), one of major nitro-fatty acids, activates Nrf2 in the same manner that of a cyclopentenone prostaglandin 15-deoxy-?(12,14) -prostaglandin J? (15d-PGJ?) 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?, 15d-PGJ? or diethylmaleate (DEM), but not with hydrogen peroxide (H?O?), when exogenous Nrf2 and Keap1 were co-overexpressed. Induction by OA-NO? or 15d-PGJ? but not DEM was observed, even when a C151S mutation was introduced in Keap1. Our results support the contention that OA-NO? and 15d-PGJ? share an analogous cysteine code as electrophiles and also have similar anti-inflammatory roles.

SUBMITTER: Tsujita T 

PROVIDER: S-EPMC4124525 | biostudies-other | 2011 Jan

REPOSITORIES: biostudies-other