Epoxide hydrolases in the rat epididymis: Possible roles in xenobiotic and endogenous fatty acid metabolism

Shelley Brown DuTeaux, John W. Newman, Christophe Morisseau, Elise A. Fairbairn, Karen Jelks, Bruce D. Hammock, Marion G. Miller

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Epoxide hydrolases play an important role in detoxifying epoxides that arise from the metabolism of xenobiotic and endogenous compounds. Both the soluble and microsomal forms of epoxide hydrolase (sEH and mEH, respectively) have been detected in the rat testis. Because of the important role the epididymis plays in sperm maturation and protection, the present study evaluated the presence and activity of these two epoxide hydrolases in the rat epididymis. Using Western blotting, protein bands consistent in size with both mEH and sEH were detected in the caput, corpus, and cauda of the epididymis. The mEH immunoreactive bands in the epididymis (∼ 50 kDa) were consistent with mEH detected in the liver and kidney. The sEH immunoreactive bands in the epididymis (∼ 65 kDa) were consistent with a recombinant sEH standard and sEH detected in the liver, kidney, and testis. The presence of mEH and sEH in the epididymis was supported by observations from substrate-based enzyme assays. Results indicated that epididymal mEH can hydrolyze [3H]-cis-stilbene oxide to the corresponding diol at levels ∼9% of the kidney. Epididymal sEH hydrolyzed the substrate [3H]-trans-diphenylpropene oxide to the corresponding diol and this activity was inhibited by cyclohexyl-dodecyl urea. Arachidonic acid epoxygenase activity was detected in epididymal S9 fractions, suggesting that fatty acid metabolism by epididymal cytochrome P450s can form epoxides that subsequently become substrates for epididymal sEH. Results from the present study indicate that the epididymis contains at least two active forms of epoxide hydrolase. The role of these enzymes in the detoxification of xenobiotic epoxides is well known, although it is unclear what cellular role they may play in the formation of biologically active metabolites in the epididymis.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalToxicological Sciences
Volume78
Issue number2
DOIs
StatePublished - Apr 2004

Fingerprint

Epoxide Hydrolases
Epididymis
Xenobiotics
Metabolism
Rats
Epoxy Compounds
Fatty Acids
Liver
Substrates
Detoxification
Enzymes
Cytochromes
Metabolites
Kidney
Oxides
Urea
Testis
Assays
Sperm Maturation
Enzyme Assays

Keywords

  • Arachidonic acid
  • Epididymis
  • Epoxide hydrolase
  • Metabolism

ASJC Scopus subject areas

  • Toxicology

Cite this

DuTeaux, S. B., Newman, J. W., Morisseau, C., Fairbairn, E. A., Jelks, K., Hammock, B. D., & Miller, M. G. (2004). Epoxide hydrolases in the rat epididymis: Possible roles in xenobiotic and endogenous fatty acid metabolism. Toxicological Sciences, 78(2), 187-195. https://doi.org/10.1093/toxsci/kfh066

Epoxide hydrolases in the rat epididymis : Possible roles in xenobiotic and endogenous fatty acid metabolism. / DuTeaux, Shelley Brown; Newman, John W.; Morisseau, Christophe; Fairbairn, Elise A.; Jelks, Karen; Hammock, Bruce D.; Miller, Marion G.

In: Toxicological Sciences, Vol. 78, No. 2, 04.2004, p. 187-195.

Research output: Contribution to journalArticle

DuTeaux, SB, Newman, JW, Morisseau, C, Fairbairn, EA, Jelks, K, Hammock, BD & Miller, MG 2004, 'Epoxide hydrolases in the rat epididymis: Possible roles in xenobiotic and endogenous fatty acid metabolism', Toxicological Sciences, vol. 78, no. 2, pp. 187-195. https://doi.org/10.1093/toxsci/kfh066
DuTeaux, Shelley Brown ; Newman, John W. ; Morisseau, Christophe ; Fairbairn, Elise A. ; Jelks, Karen ; Hammock, Bruce D. ; Miller, Marion G. / Epoxide hydrolases in the rat epididymis : Possible roles in xenobiotic and endogenous fatty acid metabolism. In: Toxicological Sciences. 2004 ; Vol. 78, No. 2. pp. 187-195.
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