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Titolo:
Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma
Autore:
Avila, MA; Berasain, C; Torres, L; Martin-Duce, A; Corrales, FJ; Yang, HP; Prieto, J; Lu, SC; Caballeria, J; Rodes, J; Mato, JM;
Indirizzi:
Univ Navarra, Dept Med Interna, Div Hepatol & Terapia Gen, Pamplona 31008,Spain Univ Navarra Pamplona Spain 31008 ol & Terapia Gen, Pamplona 31008,Spain Univ Valencia, Dept Bioquim & Biol Mol, E-46100 Burjassot, Spain Univ Valencia Burjassot Spain E-46100 Biol Mol, E-46100 Burjassot, Spain Hosp Principe Asturias, Serv Cirug, Alcala De Henares, Spain Hosp PrincipeAsturias Alcala De Henares Spain Alcala De Henares, Spain Univ So Calif, Sch Med, Ctr Dis Liver Res, Los Angeles, CA USA Univ So Calif Los Angeles CA USA Ctr Dis Liver Res, Los Angeles, CA USA Univ So Calif, Sch Med, Div Gastrointestinal Liver Dis, Dept Med, Los Angeles, CA USA Univ So Calif Los Angeles CA USA iver Dis, Dept Med, Los Angeles, CA USA Univ Barcelona, IDIBAPS, Hosp Clin, Inst Malalties Digest,Serv Hepatol, Barcelona, Spain Univ Barcelona Barcelona Spain es Digest,Serv Hepatol, Barcelona, Spain
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 6, volume: 33, anno: 2000,
pagine: 907 - 914
SICI:
0168-8278(200012)33:6<907:RMAOTM>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOSYL-L-METHIONINE; S-ADENOSYLMETHIONINE SYNTHETASE; INJURY; HOMOCYSTEINE; DISEASE; CANCER; GLUTATHIONE; HEPATOCYTES; ETHANOL; CELLS;
Keywords:
cirrhosis; DNA methylation; hepatocarcinoma; liver; methionine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Mato, JM Univ Navarra, Dept Med Interna, Div Hepatol & Terapia Gen, Pamplona 31008,Spain Univ Navarra Pamplona Spain 31008 pia Gen, Pamplona 31008,Spain
Citazione:
M.A. Avila et al., "Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma", J HEPATOL, 33(6), 2000, pp. 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 adenosyl-transferase (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 humancirrhosis and HCC. Hypermethylation of MAT1A promoter could participate inits reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione content observed in cirrhosis.

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Documento generato il 27/11/20 alle ore 02:16:02