Products of the isoprostane pathway: unique bioactive compounds and markers of lipid peroxidation.
We previously reported the discovery of prostaglandin F2-like compounds (F2-isoprostanes) formed by nonenzymatic free-radical-induced peroxidation of arachidonic acid. Quantification of F2-isoprostanes has proven to be a major advance in assessing oxidative stress status in vivo. Central in the pathway of formation of isoprostanes are prostaglandin H2-like endoperoxides, which also undergo rearrangement in vivo to form E-ring, D-ring, and thromboxane-ring compounds. E2- and D2-isoprostanes also undergo dehydration in vivo to form reactive cyclopentenone A2- and J2-isoprostanes, which are susceptible to Michael addition reactions with thiols. Recently, we described the formation of highly reactive gamma-ketoaldehydes (now termed isoketals) as products of isoprostane endoperoxide rearrangement which readily adduct to lysine residues on proteins and induce cross-links at rates that far exceed other aldehyde products of lipid peroxidation. Isoprostane-like compounds (neuroprostanes) and isoketal-like compounds (neuroketals) are formed from oxidation of docosahexaenoic acid, which is enriched in the brain, and measurement of neuroprostanes may provide a unique marker of oxidative neuronal injury.
Roberts
L Jackson
LJ
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6602, USA. jack.roberts@mcmail.vanderbilt.edu
Morrow
J D
JD
D000818:Animals; D015415:Biomarkers; D006801:Humans; D028421:Isoprostanes / Q000737:chemistry / Q000378:metabolism*; D015227:Lipid Peroxidation; D015394:Molecular Structure; D010084:Oxidation-Reduction
D015415:Biomarkers; D028421:Isoprostanes