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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorWimalasena, D. Shyamalien_US
dc.contributor.authorWiese, Thomas J.en_US
dc.contributor.authorWimalasena, Kandategeen_US
dc.date.accessioned2012-02-06T17:17:26Z
dc.date.available2012-02-06T17:17:26Z
dc.date.issued2007-04-01en_US
dc.identifier17217412en_US
dc.identifier2985190Ren_US
dc.identifierJNC4362en_US
dc.identifierNS 39423en_US
dc.identifier.citationJournal of neurochemistry. 2007 Apr; 101(2): 313-26.en_US
dc.identifier.issn0022-3042en_US
dc.identifier.urihttp://dx.doi.org/10.1111/j.1471-4159.2006.04362.xen_US
dc.identifier.urihttp://hdl.handle.net/10057/4423
dc.descriptionClick on the DOI link below to access the article.en_US
dc.description.abstractThe involvement of copper in the pathophysiology of neurodegeneration has been well documented but is not fully understood. Commonly, the effects are attributed to increased reactive oxygen species (ROS) production due to inherent redox properties of copper ions. Here we show copper can have physiological effects distinct from direct ROS production. First, we show that extragranular free copper inhibits the vesicular H(+)-ATPase of resealed chromaffin granule ghosts. Extragranular ascorbate potentiates this inhibition. The inhibition is mixed type with K(is) = 6.8 +/- 2.8 micromol/L and K(ii) = 3.8 +/- 0.6 micromol/L, with respect to ATP. Second, extracellular copper causes an inhibition of the generation of a pH-gradient and rapid dissipation of pre-generated pH and catecholamine gradients. Copper chelators and the ss-amyloid peptide 1-42 were found to effectively prevent the inhibition. The inhibition is reversible and time-independent suggesting the effects of extracellular copper on H(+)-ATPase is direct, and not due to ROS. The physiological significance of these observations was shown by the demonstration that extracellular copper causes a dramatic perturbation of dopamine metabolism in SH-SY5Y cells. Thus, we propose that the direct inhibition of the vesicular H(+)-ATPase may also contribute to the neurotoxic effects of copper.en_US
dc.description.sponsorshipNINDS NIH HHSen_US
dc.format.extent313-26en_US
dc.language.isoengen_US
dc.publisherJohn Wiley and Sonsen_US
dc.relation.ispartofseriesJournal of neurochemistryen_US
dc.relation.ispartofseriesJ. Neurochem.en_US
dc.sourceNLMen_US
dc.subjectResearch Support, N.I.H., Extramuralen_US
dc.subjectResearch Support, U.S. Gov't, Non-P.H.S.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshBrain/drug effectsen_US
dc.subject.meshCattleen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshChromaffin Granules/drug effectsen_US
dc.subject.meshCopper/toxicityen_US
dc.subject.meshDopamine/metabolismen_US
dc.subject.meshEnzyme Inhibitors/toxicityen_US
dc.subject.meshHumansen_US
dc.subject.meshHydrogen-Ion Concentration/drug effectsen_US
dc.subject.meshNeurodegenerative Diseases/drug effectsen_US
dc.subject.meshNeurons/drug effectsen_US
dc.subject.meshNeurotoxins/toxicityen_US
dc.subject.meshProton-Translocating ATPases/antagonists & inhibitorsen_US
dc.subject.meshSubcellular Fractionsen_US
dc.subject.meshBrain/metabolismen_US
dc.subject.meshBrain/physiopathologyen_US
dc.subject.meshChromaffin Granules/metabolismen_US
dc.subject.meshNeurodegenerative Diseases/metabolismen_US
dc.subject.meshNeurodegenerative Diseases/physiopathologyen_US
dc.subject.meshNeurons/metabolismen_US
dc.subject.meshNeurons/pathologyen_US
dc.subject.meshProton-Translocating ATPases/metabolismen_US
dc.titleCopper ions disrupt dopamine metabolism via inhibition of V-H+-ATPase: a possible contributing factor to neurotoxicityen_US
dc.typeArticleen_US
dc.coverage.spacialEnglanden_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 2007, John Wiley and Sonsen_US


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