Proteomic analysis of the hepatic tissue of Long-Evans Cinnamon (LEC) rats according to the natural course of Wilson disease.

Abstract

Copper-induced toxicity is important in the pathogenic process of Wilson's disease (WD). Using Long-Evans Cinnamon (LEC) rats, an animal model of WD, the study was undertaken to identify proteins involved in the process of WD and to investigate their functional roles in copper-induced hepatotoxicity. In early stages, expression levels of mitochondrial matrix proteins including agmatinase, isovaleryl coenzyme A dehydrogenase, and cytochrome b5 were downregulated. As mitochondrial injuries progressed, along with subsequent apoptotic processes, expressions of malate dehydrogenase 1, annexin A5, transferrin, S-adenosylhomocysteine hydrolase, and sulfite oxidase 1 were differentially regulated. Notably, the expression of malate dehydrogenase 1 was downregulated while the annexin A5 was overexpressed in an age-dependent manner, indicating that these proteins may be involved in the WD process. In addition, pronounced under-expression of S-adenosylhomocysteine hydrolase in elderly LEC rats, also involved in monoamine neurotransmitter metabolism, indicates that this protein might be related to the development of neurological manifestations in WD. The results of our study help to understand the pathogenic process of WD in hepatic tissues, identifying the important proteins associated with the disease process of WD, and to investigate the molecular pathogenic process underlying the development of neurological manifestations in WD.

• Authors: Beom H Lee, Jae-Min Kim, Sun H Heo, Joo H Mun, Jihun Kim, Joo H Kim, Hye Y Jin, Gu-Hwan Kim, Jin-Ho Choi, Han-Wook Yoo
• Journal: Proteomics (Proteomics) Vol. 11 Issue 18 Pg. 3698-705 (Sep 2011) ISSN: 1615-9861 [Electronic] Germany
• PMID: 21751376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Annexin A5
• Proteome
• Transferrin
• Copper
• Cytochromes b5
• Malate Dehydrogenase
• Isovaleryl-CoA Dehydrogenase
• Sulfite Oxidase
• Adenosylhomocysteinase
• Ureohydrolases
• agmatinase

Topics

• Adenosylhomocysteinase (metabolism)
• Age Factors
• Animals
• Annexin A5 (metabolism)
• Blotting, Western
• Cell Nucleus Size
• Copper (metabolism, toxicity)
• Cytochromes b5 (metabolism)
• Disease Models, Animal
• Hepatocytes (pathology)
• Hepatolenticular Degeneration (metabolism, pathology)
• Isovaleryl-CoA Dehydrogenase (metabolism)
• Liver (metabolism, pathology)
• Malate Dehydrogenase (metabolism)
• Mitochondria (metabolism)
• Proteome (analysis)
• Proteomics
• Rats
• Rats, Inbred LEC
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Sulfite Oxidase (metabolism)
• Transferrin (metabolism)
• Ureohydrolases (metabolism)