Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid

J Biol Chem. 1998 May 29;273(22):13605-12. doi: 10.1074/jbc.273.22.13605.


F2-isoprostanes are prostaglandin F2-like compounds that are formed nonenzymatically by free radical-induced oxidation of arachidonic acid. We explored whether oxidation of docosahexaenoic acid (C22:6omega3), which is highly enriched in the brain, led to the formation of F2-isoprostane-like compounds, which we term F4-neuroprostanes. Oxidation of docosahexaenoic acid in vitro yielded a series of compounds that were structurally established to be F4-neuroprostanes using a number of mass spectrometric approaches. The amounts formed exceeded levels of F2-isoprostanes generated from arachidonic acid by 3.4-fold. F4-neuroprostanes were detected esterified in normal whole rat brain and newborn pig cortex at a level of 7.0 +/- 1.4 ng/g and 13.1 +/- 8 ng/g, respectively. Furthermore, F4-neuroprostanes could be detected in normal human cerebrospinal fluid and levels in patients with Alzheimer's disease (110 +/- 12 pg/ml) were significantly higher than age-matched controls (64 +/- 8 pg/ml) (p < 0.05). F4-neuroprostanes may provide a unique marker of oxidative injury to the brain and could potentially exert biological activity. Furthermore, the formation of F4-neuroprostane-containing aminophospholipids might adversely effect neuronal function as a result of alterations they induce in the biophysical properties of neuronal membranes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Animals
  • Brain / metabolism
  • Dinoprost / analogs & derivatives
  • Dinoprost / biosynthesis*
  • Dinoprost / cerebrospinal fluid
  • Docosahexaenoic Acids / metabolism*
  • Humans
  • Mass Spectrometry
  • Rats
  • Stereoisomerism
  • Swine


  • Docosahexaenoic Acids
  • Dinoprost