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dc.contributor.authorDelgado, Miguel-
dc.contributor.authorPérez-Miguelsanz, Juliana-
dc.contributor.authorGarrido, Francisco-
dc.contributor.authorRodríguez-Tarduchy, Gemma-
dc.contributor.authorPérez-Sala, Dolores-
dc.contributor.authorPajares, María A.-
dc.date.accessioned2009-06-19T10:08:31Z-
dc.date.available2009-06-19T10:08:31Z-
dc.date.issued2008-
dc.identifier.citationCellular and Molecular Life Sciences 65(13): 2080-2090 (2008)en_US
dc.identifier.issn1420-682X-
dc.identifier.otherPMID: 18560753-
dc.identifier.urihttp://hdl.handle.net/10261/13801-
dc.descriptionEl pdf del artículo es la versión de autor.-
dc.description.abstractWilson’s disease is characterized by long-term hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model early alterations in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle were detected. Noteworthy, the main change was a redox mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases.en_US
dc.description.sponsorshipMinisterio de Educación y Ciencia (BMC2002-00243 and BFU2005-00050 to M.A.P. and SAF2006-03489 to D.P-S.) and the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (RCMN C03/08 to M.A.P.). M. D. was supported by fellowships of the RCMN C03/08 and PI05/0563 grants of the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III.en_US
dc.format.extent1789030 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherSpringeren_US
dc.rightsopenAccessen_US
dc.subjectMethionine metabolismen_US
dc.subjectMethionine adenosyltransferaseen_US
dc.subjectCopper accumulationen_US
dc.subjectWilson's diseaseen_US
dc.subjectS-adenosylhomocysteine hydrolaseen_US
dc.subjectGlutathioneen_US
dc.titleEarly effects of copper accumulation on methionine metabolismen_US
dc.typeartículoen_US
dc.identifier.doi10.1007/s00018-008-8201-4-
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://dx.doi.org/10.1007/s00018-008-8201-4en_US
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