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Review
. 2018 Mar 19:S1089-8603(17)30323-3.
doi: 10.1016/j.niox.2018.03.012. Online ahead of print.

Regulation of stress signaling pathways by nitro-fatty acids

Ashik Jawahar Deen  1 , Virve Sihvola  1 , Jouni Härkönen  1 , Tommi Patinen  1 , Simone Adinolfi  1 , Anna-Liisa Levonen  2
Affiliations
Review

Regulation of stress signaling pathways by nitro-fatty acids

Ashik Jawahar Deen et al. Nitric Oxide. .

Abstract

Electrophilic nitrated-fatty acids (NO2-FA, nitroalkenes) are formed during reactions of NO-derived oxidized species (•NO, •NO2) with either free or esterified polyunsaturated fatty acids. Due to their electrophilic character, they react with nucleophiles such as cysteine thiols in signaling proteins, thereby triggering downstream signaling cascades. Herein, we review two stress-signaling pathways activated by nitroalkenes, the KEAP1-NRF2 signaling pathway and the heat shock response (HSR) pathway. In addition, their biological and pharmacological relevance are discussed. Given that perturbations in both proteostasis and redox balance are common in many disease processes, dual activation of both pathways by nitroalkenes is a promising pharmacological approach for their treatment.

Keywords: HSF1; KEAP1; NO(2)-FA; NRF2; Redox signaling.

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