15-Deoxy-Delta(12,14)-prostaglandin J2: an electrophilic trigger of cellular responses

Abstract

Electrophilic molecules are endogenously generated and are causally involved in many pathophysiological effects. Prostaglandin D (20 (PGD (2)), a major cyclooxygenase product in a variety of tissues, readily undergoes dehydration to yield the cyclopentenone-type PGs of the J (2)-series such as 15-deoxy-Delta (12,14)-PGJ (2) (15d-PGJ (2)). 15d-PGJ (2) is an electrophile, which can covalently react via the Michael addition reaction with nucleophiles, such as the free sulfhydryls of glutathione and cysteine residues in cellular proteins that play an important role in the control of the redox cell-signaling pathways. Covalent binding of 15d-PGJ (2) to cellular proteins may be one of the mechanisms by which 15d-PGJ (2) induces a cellular response involved in most of the pathophysiological effects associated with inflammation. In the present perspective, we provide a comprehensive summary of 15d-PGJ (2) as an electrophilic mediator of cellular responses.