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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Veröffentlicht in:Journal of hepatology 2000-12, Vol.33 (6), p.907-914
Hauptverfasser: Avila, Matías A, Berasain, Carmen, Torres, Luis, Martín-Duce, Antonio, Corrales, Fernando J, Yang, Heping, Prieto, Jesús, Lu, Shelly C, Caballería, Juan, Rodés, Juan, Mato, José M
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container_end_page 914
container_issue 6
container_start_page 907
container_title Journal of hepatology
container_volume 33
creator Avila, Matías A
Berasain, Carmen
Torres, Luis
Martín-Duce, Antonio
Corrales, Fernando J
Yang, Heping
Prieto, Jesús
Lu, Shelly C
Caballería, Juan
Rodés, Juan
Mato, José M
description 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 β-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.
doi_str_mv 10.1016/S0168-8278(00)80122-1
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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 β-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.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/S0168-8278(00)80122-1</identifier><identifier>PMID: 11131452</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Carcinoma, Hepatocellular - metabolism ; Cirrhosis ; DNA methylation ; Enzymes - genetics ; Hepatocarcinoma ; Humans ; Isoenzymes - genetics ; Liver ; Liver - metabolism ; Liver Cirrhosis - metabolism ; Liver Neoplasms - metabolism ; Methionine ; Methionine - metabolism ; Methionine Adenosyltransferase - genetics ; Methylation ; Promoter Regions, Genetic - physiology ; RNA, Messenger - metabolism</subject><ispartof>Journal of hepatology, 2000-12, Vol.33 (6), p.907-914</ispartof><rights>2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-e6d0acc75657d7bcd97f31c8bd4ed544803afba13b6b98c83d310c89cc5d591f3</citedby><cites>FETCH-LOGICAL-c460t-e6d0acc75657d7bcd97f31c8bd4ed544803afba13b6b98c83d310c89cc5d591f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0168-8278(00)80122-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11131452$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Avila, Matías A</creatorcontrib><creatorcontrib>Berasain, Carmen</creatorcontrib><creatorcontrib>Torres, Luis</creatorcontrib><creatorcontrib>Martín-Duce, Antonio</creatorcontrib><creatorcontrib>Corrales, Fernando J</creatorcontrib><creatorcontrib>Yang, Heping</creatorcontrib><creatorcontrib>Prieto, Jesús</creatorcontrib><creatorcontrib>Lu, Shelly C</creatorcontrib><creatorcontrib>Caballería, Juan</creatorcontrib><creatorcontrib>Rodés, Juan</creatorcontrib><creatorcontrib>Mato, José M</creatorcontrib><title>Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>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 β-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.</description><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Cirrhosis</subject><subject>DNA methylation</subject><subject>Enzymes - genetics</subject><subject>Hepatocarcinoma</subject><subject>Humans</subject><subject>Isoenzymes - genetics</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver Cirrhosis - metabolism</subject><subject>Liver Neoplasms - metabolism</subject><subject>Methionine</subject><subject>Methionine - metabolism</subject><subject>Methionine Adenosyltransferase - genetics</subject><subject>Methylation</subject><subject>Promoter Regions, Genetic - physiology</subject><subject>RNA, Messenger - metabolism</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtv1DAQgK0KRLeFn1DkE2oPgXGezglVVV9SBVKBs-WMJ4pRbC92slI58stJuis49uKxPN_MeD7GzgR8FCDqT9-WQ2Yyb-Q5wIUEkeeZOGIbUQNkUJfiFdv8Q47ZSUo_AaCAtnzDjoUQhSirfMP-PJKZkQx3j18uue5mb7RH4qHn00Dcaes5-d9PjhK3fhfG3cIub46mwQZvPa1X3YXRJrcmhtlpz0e7o8jRxjiEZBPX3vCBtnoKSOM4j3pJ6ojWB6ffste9HhO9O8RT9uPm-vvVXfbw9fb-6vIhw7KGKaPagEZsqrpqTNOhaZu-ECg7U5KpylJCoftOi6Kru1aiLEwhAGWLWJmqFX1xyj7s-25j-DVTmpSzaf2O9hTmpJq8ynOQYgGrPYgxpBSpV9tonY5PSoBa5atn-Wo1qwDUs3y11r0_DJg7R-Z_1cH2AnzeA7SsubMUVUJLi25jI-GkTLAvjPgLxDaW7g</recordid><startdate>20001201</startdate><enddate>20001201</enddate><creator>Avila, Matías A</creator><creator>Berasain, Carmen</creator><creator>Torres, Luis</creator><creator>Martín-Duce, Antonio</creator><creator>Corrales, Fernando J</creator><creator>Yang, Heping</creator><creator>Prieto, Jesús</creator><creator>Lu, Shelly C</creator><creator>Caballería, Juan</creator><creator>Rodés, Juan</creator><creator>Mato, José M</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20001201</creationdate><title>Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma</title><author>Avila, Matías A ; 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subjects Carcinoma, Hepatocellular - metabolism
Cirrhosis
DNA methylation
Enzymes - genetics
Hepatocarcinoma
Humans
Isoenzymes - genetics
Liver
Liver - metabolism
Liver Cirrhosis - metabolism
Liver Neoplasms - metabolism
Methionine
Methionine - metabolism
Methionine Adenosyltransferase - genetics
Methylation
Promoter Regions, Genetic - physiology
RNA, Messenger - metabolism
title Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma
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