Glutathione promotes prostaglandin H synthase (cyclooxygenase)-dependent formation of malondialdehyde and 15(S)-8-iso-prostaglandin F2α

Prostaglandin (PG) H synthases (PGHS) or cyclooxygenases (COX) catalyse the peroxidation of arachidonic acid (AA) to PGG(2) and PGH(2) which are further converted to a series of prostaglandins and thromboxane A(2). Here, we report that GSH promotes concomitant formation of the current oxidative stress biomarkers malondialdehyde (MDA) and 15(S)-8-iso-prostaglandin F-2 alpha from AA via PGHS. This illustrates an uncommon interplay of enzymatic and chemical reactions to produce species that are considered to be exclusively produced by free-radical-catalysed reactions. We propose mechanisms for the PGHS/AA/GSH-dependent formation of MDA, 15(S)-8-iso-prostaglandin F-2 alpha and other F-2-isoprostanes. These mechanisms are supported by clinical observations. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.