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Soluble Epoxide Hydrolase Inhibition Modulates Gene Expression of Anti‐Apoptotic and Apoptotic Factors
Author(s) -
Simpkins Alexis N,
Elmarakby Ahmed A.,
Quigley Jeffery E.,
Schreihofer Derek A.,
Hammock Bruce D.,
Imig John D.
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.733.11
Subject(s) - epoxide hydrolase 2 , apoptosis , gene expression , downregulation and upregulation , gene , aldehyde dehydrogenase , chemistry , pharmacology , biology , biochemistry , microbiology and biotechnology , enzyme
Epoxyeicosatrienoic acids cerebral protective properties are attenuated by degradation to less active diols by the soluble epoxide hydrolase enzyme. We previously demonstrated that chronic SEH inhibition via adamantanyl dodecanoic acid (AUDA) protects against cerebral ischemia. Here we test the hypothesis that AUDA provides neural protection via altering gene expression of apoptotic and anti‐apoptotic factors. We compared expression of 30 anti‐apoptotic and 54 apoptotic genes in brain samples collected from controls and AUDA treated (2mg/day, 6weeks) SHRSPs and WKYs using an apoptosis PCR microarray (n=3 per group). Gene expression of 18 apoptotic and 8 anti‐apoptotic factors increased ≥2 fold in SHRSP control versus (vs) WKY control. While AUDA treated SHRSP had only 1 upregulated apoptotic gene ≥2 fold vs WKY control. Also, AUDA reduced gene expression of 29 apoptotic and 8 anti‐apoptotic factors ≥1.48 fold in SHRSP vs SHRSP control. In contrast, gene expression of 8 anti‐apoptotic and 14 of apoptotic factors increased ≥1.48 fold in AUDA treated WKY vs WKY control. Interestingly, AUDA increased gene expression of anti‐apoptotic Mapk8ip in SHRSPs and WKYs, which is reportedly neural protective in ischemia. These results suggest that SEH inhibition is neural protective due to dampening of apoptotic gene expression in SHRSPs and upregulation of anti‐apoptotic gene expression in WKYs and SHRSPs. (AHA and NIH)