15-Deoxy-Δ12,14-prostaglandin J2 as an electrophilic mediator

Lipid-derived electrophilic molecules are endogenously generated and are causally involved in many pathophysiological effects. Prostaglandin D-2, a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the J-series PGs such as 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)). Because of the electrophilic ,-unsaturated ketone moiety present in its cyclopentenone ring, 15d-PGJ(2) acts as an endogenous electrophile. 15d-PGJ(2) can covalently react via the Michael addition reaction with critical cellular nucleophiles, such as the free cysteine residues of proteins that play a key role in the regulation of the intracellular signaling pathways. Covalent modification of cellular proteins by 15d-PGJ(2) may be one of the most important mechanisms by which 15d-PGJ(2) induces many biological responses involved in the pathophysiological effects associated with inflammation. This current review is intended to provide a comprehensive summary of 15d-PGJ(2) as an endogenous electrophilic mediator of biological activities.