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JHC exPRESS: First Published March 3, 2008. doi:10.1369/jhc.2008.950659
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A more recent version of this article appeared on June 1, 2008.
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Articles

Distribution and Expression of Soluble Epoxide Hydrolase in Human Brain

Priyanka Sura 1, Radhakrishna Sura 1, Ahmed E. EnayetAllah 1 and David F. Grant 1*

1 Department of Pharmaceutical Sciences (PS,AEE,DFG), and Department of Pathobiology and Veterinary Science (RS), University of Connecticut, Storrs, Connecticut

* To whom correspondence should be addressed. E-mail: david.grant{at}uconn.edu.

Submitted on December 20, 2007
Accepted on 11 February 2008


  Abstract
Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid, which function in the brain to regulate cerebral blood flow as well as protect against ischemic brain injury. EETs are converted by soluble epoxide hydrolase (sEH) to the corresponding inactive diol metabolites. Previous animal studies have indicated that sEH gene deletion or treatment with sEH inhibitors results in increased levels of EETs and protection against stroke induced brain damage. To begin elucidating the underlying mechanism for these effects, we sought to determine the distribution, expression and activity of sEH in human brain samples obtained from patients with no neurological changes/pathologies. Immunohistochemical analyses demonstrated the distribution of sEH mainly in the neuronal cell bodies, oligodendrocytes and scattered astrocytes. Surprisingly, in the choroid plexus, sEH was found to be highly expressed in ependymal cells. Vascular localization of sEH was evident in several regions, where it was highly expressed in the smooth muscles of the arterioles. Western Blot analysis and enzyme assays confirmed the presence of sEH in the normal brain. Our results indicate differential localization of sEH in the human brain, thus suggestive of an essential role for this enzyme in the central nervous system. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Key Words: soluble epoxide hydrolase, epoxyeicosatrienoic acids, central nervous system, cerebral blood flow, cytochrome P450 epoxygenase


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