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

• Published in: FEBS letters 2012-10, Vol.586 (20), p.3723-3730
• Main Authors: Tsikas, Dimitrios, Suchy, Maria-Theresia, Niemann, Jonas, Tossios, Paschalis, Schneider, Yessica, Rothmann, Sabine, Gutzki, Frank-Mathias, Frölich, Jürgen C., Stichtenoth, Dirk O.
• Format: Article
• Language: English
• Subjects: Aged; Animals; Arachidonic acid; Arachidonic Acid - metabolism; Biomarker; Cyclooxygenase; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Dinoprost - analogs & derivatives; Dinoprost - biosynthesis; Female; Glutathione; Glutathione - pharmacology; Humans; Male; Malondialdehyde - metabolism; Oxidative stress; Prostaglandin H synthase; Sheep
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.09.001

► Cyclooxygenases (COX) convert arachidonic acid to MDA and 15(S)-8-iso-PGF2α. ► Glutathione (GSH) promotes COX-dependent MDA and 15(S)-8-iso-PGF2α formation. ► Mechanisms are proposed for the formation of MDA and 15(S)-8-iso-PGF2α. ► The utility of MDA and 15(S)-8-iso-PGF2α as oxidative stress biomarkers is challenged. Prostaglandin (PG) H synthases (PGHS) or cyclooxygenases (COX) catalyse the peroxidation of arachidonic acid (AA) to PGG2 and PGH2 which are further converted to a series of prostaglandins and thromboxane A2. Here, we report that GSH promotes concomitant formation of the current oxidative stress biomarkers malondialdehyde (MDA) and 15(S)-8-iso-prostaglandin F2α 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 F2α and other F2-isoprostanes. These mechanisms are supported by clinical observations.