Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma

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 met...

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Detalles Bibliográficos
Autores: Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f, Berasain-Lasarte, C. (Carmen)|||/items/f1d61c19-1753-4442-a3fd-cc90220e84a0, Torres, L. (Luis)|||/items/e4740a05-e8bb-4f09-b3ca-e119dae6742b, Martin-Duce, A. (Antonio)|||/items/38618fd4-155c-4043-97ec-35b500f9c390, Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2, Yang, H. (Heping)|||/items/6584e4bc-a102-46e3-8eeb-b72d30d80e07, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71, Lu, S.C. (Shelly C.)|||/items/e4a2a6d5-e196-42c9-b95b-2a670ce9a801, Caballeria, J. (Juan)|||/items/56e3d84d-13f7-4138-b036-ec725cc9a622, Rodes, J. (Juan)|||/items/e075482e-6f85-4800-9294-86cca61fd0fe, Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Tipo de recurso: artículo
Fecha de publicación:2000
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/21343
Acceso en línea:https://hdl.handle.net/10171/21343
Access Level:acceso abierto
Palabra clave:Cirrhosis
DNA methylation
Hepatocarcinema
Liver
Methionine
Descripción
Sumario: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.

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