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Molecular changes in the cytochrome P450 4A isoforms in the Sprague Dawley rat kidney following ischemia/reperfusion
Author(s) -
Akbulut Talha,
Steinman Averia,
Roman Richard J.,
Park Frank
Publication year - 2008
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.22.1_supplement.730.10
Subject(s) - kidney , ischemia , endocrinology , medicine , cytochrome p450 , gene isoform , messenger rna , western blot , reperfusion injury , chemistry , biology , metabolism , biochemistry , gene
20‐HETE is a major eicosanoid in the kidney, but little is known about the molecular regulation of the enzymes that produce this molecule in the kidney following ischemia‐reperfusion (I/R) injury. We designed the following study to determine the changes in the cytochrome P450 4A isoforms, specifically CYP4A1, 4A2, 4A3, and 4A8, following I/R in uninephrectomized Sprague Dawley (SD) rats. SD rats were sham‐operated or exposed to ischemia by clamping of renal artery and vein for 45 minutes, and then reperfused for 1, 3 or 7 days. Medullary CYP4A protein levels determined by Western blot analysis started to decrease 1 day after reperfusion and reduction levels reached to ~10% (P<0.01; n=5) of the control levels at day 3 post‐I/R. No changes in the cortical protein levels were detected. To determine the mRNA changes in the medulla, quantitative RT‐PCR was performed. CYP4A2, CYP4A3 and CYP4A8 mRNA levels decreased significantly following I/R, and reached their nadir at day 3 post‐I/R between 74–93% (P<0.05). These findings would suggest that CYP4A isoforms are differentially regulated in the kidney following I/R and may have a possible role in mediating biological effects in response to this type of injury.