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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma
Authors: Avila, M.A. (Matías Antonio)
Berasain, C. (Carmen)
Torres, L. (Luis)
Martin-Duce, A. (Antonio)
Corrales, F.J. (Fernando José)
Yang, H. (Heping)
Prieto, J. (Jesús)
Lu, S.C. (Shelly C.)
Caballeria, J. (Juan)
Rodes, J. (Juan)
Mato, J.M. (José María)
Keywords: Cirrhosis
DNA methylation
Hepatocarcinema
Liver
Methionine
Issue Date: 2000
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0168827800801221
ISSN: 0168-8278
Citation: Avila MA, Berasain C, Torres L, Martin-Duce A, Corrales FJ, Yang H, et al. Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 2000 Dec;33(6):907-914.
Abstract
BACKGROUND/AIMS: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood. In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyltransferase (MAT1A), glycine methyltransferase (GNMT), methionine synthase (MS), betaine homocysteine methyltransferase (BHMT) and cystathionine beta-synthase (CBS) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. METHODS: The expression of the above-mentioned genes was determined by quantitative RT-PCR analysis. Methylation of MAT1A promoter was assessed by methylation-sensitive restriction enzyme digestion of genomic DNA. RESULTS: When compared to normal livers MAT1A, GNMT, BHMT, CBS and MS mRNA contents were significantly reduced in liver cirrhosis. Interestingly, MAT1A promoter was hypermethylated in the cirrhotic liver. HCC tissues also showed decreased mRNA levels of these enzymes. CONCLUSIONS: These findings establish that the abundance of the mRNA of the main genes involved in methionine metabolism is markedly reduced in human cirrhosis and HCC. Hypermethylation of MAT1A promoter could participate in its reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione content observed in cirrhosis.
Permanent link: http://hdl.handle.net/10171/21343
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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