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Nitro‐fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1‐Nrf2 system: a study using green fluorescent protein transgenic zebrafish
Author(s) -
Tsujita Tadayuki,
Li Li,
Nakajima Hitomi,
Iwamoto Noriko,
NakajimaTakagi Yaeko,
Ohashi Ken,
Kawakami Koichi,
Kumagai Yoshito,
Freeman Bruce A.,
Yamamoto Masayuki,
Kobayashi Makoto
Publication year - 2011
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01466.x
Subject(s) - green fluorescent protein , keap1 , zebrafish , cyclopentenone , biology , biochemistry , fatty acid , transgene , polyunsaturated fatty acid , gene , chemistry , stereochemistry , transcription factor
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.