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Cerebral vascular cytochrome P‐450 4A enzyme activity and expression are elevated in a genetic model of stroke
Author(s) -
Dunn Kathryn M. J.,
Roman Richard J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1383-c
Subject(s) - medicine , western blot , endocrinology , arachidonic acid , pathogenesis , downregulation and upregulation , chemistry , cytochrome p450 , locus (genetics) , gene expression , stroke (engine) , enzyme , gene , biochemistry , metabolism , mechanical engineering , engineering
Jeffs et. al identified a genetic locus on chromosome 5 that is linked to infarct size following MCAO in SHRSP rats. Contained within this QTL are the cytochrome P‐450 4A ω‐hydroxylase genes which catalyze the formation of the vasoconstrictor 20‐HETE from arachidonic acid (AA). Our lab has previously shown a role for 20‐HETE in the pathogenesis of both hemorrhagic and ischemic models of stroke. The purpose of this study was to measure cerebral vascular 20‐HETE formation and CYP4A expression in SHRSP rats compared to stroke‐resistant WKY and SHR strains. 20‐HETE formation was quantified using triple quadrupole liquid chromatography mass spectrometry (LC/MS/MS). CYP4A protein expression was analyzed by western blot. Results indicate 20‐HETE formation is significantly elevated in SHRSP rats relative to WKY and SHR (WKY 0.2237±0.0309 pmol/min/mg protein, n=6; SHR 0.3027±0.0459, n=5; SHRSP 0.3854±0.0368, n=5). Western blot analysis indicates significant elevation of CYP4A protein expression in SHRSP rats compared to WKY rats. Upregulation of cerebral vascular CYP4A expression and 20‐HETE formation may contribute to sensitivity to cerebral ischemia in SHRSP rats. This study was supported in part by National Heart, Lung, and Blood Institute Grants HL‐59996 and HL‐29587 .