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dc.contributor.authorOien, Derek B.
dc.contributor.authorOrtiz, Andrea Naomi
dc.contributor.authorRittel, Alexander G.
dc.contributor.authorDobrowsky, Rick T.
dc.contributor.authorJohnson, Michael A.
dc.contributor.authorLevant, Beth
dc.contributor.authorFowler, Stephen C.
dc.contributor.authorMoskovitz, Jackob
dc.date.accessioned2017-05-16T16:24:55Z
dc.date.available2017-05-16T16:24:55Z
dc.date.issued2010-07
dc.identifier.citationOien, D. B., Ortiz, A. N., Rittel, A. G., Dobrowsky, R. T., Johnson, M. A., Levant, B., … Moskovitz, J. (2010). Dopamine D2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse. Journal of Neurochemistry, 114(1), 51–61. http://doi.org/10.1111/j.1471-4159.2010.06721.xen_US
dc.identifier.urihttp://hdl.handle.net/1808/24222
dc.description.abstractPrevious research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio-behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D2-receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed, protein expression levels of dopamine D2-receptor were higher in knockout mice compared with wild-type. However, the binding of dopamine D2-receptor agonist was compromised in the same fractions of knockout mice. Coupling efficiency of dopamine D2-receptors to G-proteins was also significantly reduced in knockout mice, supporting the compromised agonist binding. Furthermore, pre-synaptic dopamine release in knockout striatal sections was less responsive than control sections to dopamine D2-receptor ligands. Behaviorally, the locomotor activity of knockout mice was less responsive to the inhibitory effect of quinpirole than wild-type mice. Involvement of specific methionine residue oxidation in the dopamine D2-receptor third intracellular loop is suggested by in vitro studies. We conclude that ablation of methionine sulfoxide reductase can affect dopamine signaling through altering dopamine D2-receptor physiology and may be related to symptoms associated with neurological disorders and diseases.en_US
dc.publisherWileyen_US
dc.rightsThis is the peer reviewed version of the following article: Oien, D. B., Ortiz, A. N., Rittel, A. G., Dobrowsky, R. T., Johnson, M. A., Levant, B., Fowler, S. C. and Moskovitz, J. (2010), Dopamine D2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse. Journal of Neurochemistry, 114: 51–61. , which has been published in final form at http://doi.org/10.1111/j.1471-4159.2010.06721.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en_US
dc.subjectDopamineen_US
dc.subjectDopamine receptoren_US
dc.subjectLocomotor activityen_US
dc.subjectMethionine oxidationen_US
dc.subjectOxidative stressen_US
dc.subjectPost-translation modificationen_US
dc.titleDopamine D2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouseen_US
dc.typeArticleen_US
kusw.kuauthorOien, Derek B.
kusw.kuauthorOrtiz, Andrea N.
kusw.kuauthorRittel, Alexander G.
kusw.kuauthorDobrowsky, Rick T.
kusw.kuauthorJohnson, Michael A.
kusw.kuauthorFowler, Stephen C.
kusw.kuauthorMoskovitz, Jackob
kusw.kudepartmentPharmacyen_US
kusw.kudepartmentChemistryen_US
dc.identifier.doi10.1111/j.1471-4159.2010.06721.xen_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC2933736en_US
dc.rights.accessrightsopenAccess


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