Regulation of stress signaling pathways by nitro-fatty acids

Ashik Jawahar Deen; Virve Sihvola; Jouni Härkönen; Tommi Patinen; Simone Adinolfi; Anna-Liisa Levonen

doi:10.1016/j.niox.2018.03.012

Regulation of stress signaling pathways by nitro-fatty acids

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

Authors

Ashik Jawahar Deen¹, Virve Sihvola¹, Jouni Härkönen¹, Tommi Patinen¹, Simone Adinolfi¹, Anna-Liisa Levonen²

Affiliations

¹ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio FI-70211, Finland.
² A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio FI-70211, Finland. Electronic address: anna-liisa.levonen@uef.fi.

PMID: 29567143
DOI: 10.1016/j.niox.2018.03.012

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.

Publication types

Review