Distribution of soluble epoxide hydrolase and of cytochrome P450 2C8, 2C9, and 2J2 in human tissues.
Soluble epoxide hydrolase (sEH) hydrolyzes a wide variety of endogenous and exogenous epoxides. Many of these epoxides are believed to be formed by cytochrome P450 epoxygenases. Here we report the distribution of sEH and cytochrome P450 epoxygenases 2C8, 2C9, and 2J2 by immunohistochemistry. A large number of different tissues from different organs were evaluated using high-throughput tissue microarrays. sEH was found in the liver, kidney, and in many other organs, including adrenals, pancreatic islets, pituitary gland, lymphoid tissues, muscles, certain vascular smooth muscles, and epithelial cells in the skin, prostatic ducts, and the gastrointestinal tract. Immunolabeling for sEH was highly specific for particular tissues and individual cell types. CYP2C9 was also found in almost all of these organs and tissues, suggesting that 2C9 and sEH are very similar in their tissue-specific patterns of expression. CYP2C8 and 2J2 were also widely distributed in human tissues but were less frequently associated with sEH. The results suggest potentially distinct pathways of endogenous fatty acid epoxide production and hydrolysis in a variety of human tissues.
Enayetallah
Ahmed E
AE
Department of Pharmaceutical Sciences and Pathobiology, University of Connecticut, Storrs, Connecticut 06269, USA.
French
Richard A
RA
Thibodeau
Michael S
MS
Grant
David F
DF
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002460:Cell Line; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004851:Epoxide Hydrolases / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009928:Organ Specificity; D010105:Oxygenases / Q000378:metabolism*; D012995:Solubility
D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D000090762:Cytochrome P-450 CYP2J2; D004851:Epoxide Hydrolases