Signaling actions of electrophiles: anti-inflammatory therapeutic candidates.

Molecular Interventions
Alison L Groeger, Bruce A Freeman

Abstract

Over the past several years, research on biologically relevant electrophiles has been replete with new insights, expanding our understanding of the roles electrophiles play in vivo. Importantly, many electrophiles can form reversible covalent adducts with both proteins and small-molecule thiols in cells. This post-translational protein modification has important ramifications, including changes in protein enzymatic activity, the transduction of signals within and between cells, and alterations in gene expression. Electrophiles modulate a variety of cellular signaling processes that are involved in several major diseases with inflammatory components. The electrophilic fatty-acid derivatives discussed in this work are naturally occurring products of redox reactions and enzymatic activity. Furthermore, several of these electrophilic species and their derivatives represent potential therapeutic candidates.

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