Nitro-fatty Acids and Cyclopentenone Prostaglandins Share Strategies to Activate the Keap1-Nrf2 System: a Study Using Green Fluorescent Protein Transgenic Zebrafish

Overview

Journal Genes Cells

Specialties Cell Biology
Molecular Biology

Date 2010 Dec 15

PMID 21143560

Citations 41

Authors

Tadayuki Tsujita

Li Li

Hitomi Nakajima

Noriko Iwamoto

Yaeko Nakajima-Takagi

Ken Ohashi

Koichi Kawakami

Yoshito Kumagai

Bruce A Freeman

Masayuki Yamamoto

Makoto Kobayashi

Affiliations

Soon will be listed here.

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-Δ(12,14) -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.

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