Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Pathol. 2005 Nov;167(5):1371-7.

Absence of 12/15 lipoxygenase reduces brain oxidative stress in apolipoprotein E-deficient mice.

Author information

  • 1Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, John Morgan Building, Room 124, Philadelphia, PA 19104, USA.

Abstract

The enzyme 12/15 lipoxygenase (12/15LO) has been implicated in the oxidative modification of lipoproteins and phospholipids in vivo. In addition, mice deficient in apolipoprotein E (ApoE-/-) are characterized by spontaneous hypercholesterolemia and a systemic increase in oxidative stress. Whereas the absence of 12/15LO reduces lipid peroxidation in the plasma and urine of ApoE-/- mice, the relative contribution of this enzyme to oxidative stress in the central nervous system remains unknown. Here, we provide the first in vivo evidence that 12/15LO modulates brain oxidative stress reactions using ApoE-/- mice crossbred with 12/15LO-deficient (12/15LO-/-) mice (12/15LO-/-/ApoE-/-). In chow-fed 12-month-old 12/15LO-/-/ApoE-/- mice, the amount of brain isoprostane iPF2alpha-VI, a marker of lipid peroxidation, and carbonyls, markers of protein oxidation, were significantly reduced when compared with 12/15LO-expressing controls (12/15LO+/+/ApoE-/-). These results were observed despite the fact that cholesterol, triglyceride, and lipoprotein levels were similar to those of ApoE-/- mice. These data indicate a functional role for 12/15LO in the modulation of oxidative reactions in the central nervous system, supporting the hypothesis that inhibition of this enzymatic pathway may be a novel therapeutic target in clinical settings involving increased brain oxidative stress.

PMID:
16251421
[PubMed - indexed for MEDLINE]
PMCID:
PMC1603776
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk