title: Glutathione promotes prostaglandin H synthase (cyclooxygenase)-dependent formation of malondialdehyde and 15(S)-8-iso-prostaglandin F2α.
abstract: 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(2α) 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(2α) and other F(2)-isoprostanes. These mechanisms are supported by clinical observations.
authors.affiliation: Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany. tsikas.dimitros@mh-hannover.de
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Maria-Theresia
authors.initials: MT
authors.lastname: Suchy
authors.forename: Jonas
authors.initials: J
authors.lastname: Niemann
authors.forename: Paschalis
authors.initials: P
authors.lastname: Tossios
authors.forename: Yessica
authors.initials: Y
authors.lastname: Schneider
authors.forename: Sabine
authors.initials: S
authors.lastname: Rothmann
authors.forename: Frank-Mathias
authors.initials: FM
authors.lastname: Gutzki
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Frölich
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Stichtenoth
mesh_terms: D000368:Aged; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000096:biosynthesis; D005260:Female; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D012756:Sheep
chemical_list: C075750:8-epi-prostaglandin F2alpha; D016718:Arachidonic Acid; D008315:Malondialdehyde; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005978:Glutathione