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- Title
Early effects of copper accumulation on methionine metabolism.
- Authors
Delgado, M; Pérez-Miguelsanz, J; Garrido, F; Rodríguez-Tarduchy, G; Pérez-Sala, D; Pajares, M A
- Abstract
Wilson's disease is characterized by longterm 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 were detected in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle. Notably, 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.
- Publication
Cellular and molecular life sciences : CMLS, 2008, Vol 65, Issue 13, p2080
- ISSN
1420-682X
- Publication type
Journal Article
- DOI
10.1007/s00018-008-8201-4