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Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment.

Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. Research Abstract Details 

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  • Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. Abstract Text:

    Parkinson's disease (PD) is the most prevalent neurodegenerative movement disorder. Epidemiological studies have suggested most cases of PD are linked to environmental risk factors. Microsomal epoxide hydrolase (mEH) is a conserved enzyme that catalyzes hydrolysis of a large number of epoxide intermediates such as drugs and epoxides of environmental toxins. We hypothesize that changes in mEH are involved in the pathogenesis of PD by modulating the vulnerability of dopaminergic neurons to environmental stress. Herein we reported that acute treatment with the neurotoxin MPTP (1-methyl-4-phemyl-1,2,3,6-tetrahydropyridine) markedly increased the mEH immunoreactivity in the nigrostriatal system of C57BL/6 mice. Next, mEH knockout (KO) mice were used, and we found that tyrosine hydroxylase (TH)-positive cell loss was significantly lower in the substantia nigra of mEH KO mice compared with wild-type (WT) mice after MPTP treatment. The mean dopamine turnover ratios were significantly increased in MPTP-treated mEH KO mice compared with WT. In addition, TH is the rate-limiting enzyme for dopamine biosynthesis, and its activity is mainly regulated by TH phosphorylation at Ser-31 (pSer31) and Ser-40 (pSer40). Double immunofluorescence showed that both pSer31 and pSer40 are completely colocalized in total TH-positive cells. However, immunoblotting confirmed that there was a significantly higher level of pSer31 in mEH-KO mice when compared with WT mice after MPTP, and no marked differences among TH and its phosphorylation levels occurred after saline injection. These data suggested that mEH deficiency facilitates TH phosphorylation in the nigrostriatal dopamine system, which may be associated with an increased resistance of dopaminergic neurons to environmental toxins. (c) 2008 Wiley-Liss, Inc.

    Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. Publishing Authors By Initials

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    Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Journal of neuroscience research

    VOLUME: 86

    Page Numbers: 2792-801

    Journal Abbreviation: J. Neurosci. Res.

    ISSN: 1097-4547

    DAY: 22

    MONTH: Sep

    YEAR: 2008

    Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. Information

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    LANGUAGE: eng

    NlmUniqueID: 7600111

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    Grant and Affiliation Information for Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment.

    AFFILIATION: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Neurosci Res

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