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

Authors

  • Beom H. Lee,

    1. Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
    2. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    3. Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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  • Jae-Min Kim,

    1. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Sun H. Heo,

    1. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Joo H. Mun,

    1. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Jihun Kim,

    1. Department of Pathology, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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  • Joo H. Kim,

    1. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Hye Y. Jin,

    1. Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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  • Gu-Hwan Kim,

    1. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    2. Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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  • Jin-Ho Choi,

    1. Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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  • Han-Wook Yoo

    Corresponding author
    1. Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
    2. Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    3. Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
    • Genome Research Center for Birth defects and Genetic Diseases, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 388-1 Pungnap-Dong, Songpa-Gu, Seoul 138-736, Korea Fax: +82-2-473-3725
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  • Colour Online: See the article online to view Figs. 1, 2 in colour.

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.

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