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

FEBS Lett. 2012 Oct 19;586(20):3723-30. doi: 10.1016/j.febslet.2012.09.001. Epub 2012 Sep 13.

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.

MeSH terms

  • Aged
  • Animals
  • Arachidonic Acid / metabolism
  • Cyclooxygenase 1 / metabolism*
  • Cyclooxygenase 2 / metabolism*
  • Dinoprost / analogs & derivatives*
  • Dinoprost / biosynthesis
  • Female
  • Glutathione / pharmacology*
  • Humans
  • Male
  • Malondialdehyde / metabolism*
  • Sheep

Substances

  • 8-epi-prostaglandin F2alpha
  • Arachidonic Acid
  • Malondialdehyde
  • Dinoprost
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Glutathione