Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine
Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III activity and MAT1A expression are compromised under pathological...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2001 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/21383 |
| Acceso en línea: | https://hdl.handle.net/10171/21383 |
| Access Level: | acceso abierto |
| Palabra clave: | Liver damage Methionine metabolism Polycyclic aromatic hydrocarbons S-adenosylmethionine Methionine adenosyltransferase |
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Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionineCarretero, M.V. (M. Victoria)|||/items/32989e88-e020-4ae5-befe-dcd0b529664bLatasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356Ruiz Garcia-Trevijano, E. (Elena)|||/items/bc37b3f6-83de-42b9-bb68-e90d1296c35cCorrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2Wagner, C. (Conrad)|||/items/62a28aa8-a141-407d-a9f5-1e3427145bb1Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419fLiver damageMethionine metabolismPolycyclic aromatic hydrocarbonsS-adenosylmethionineMethionine adenosyltransferaseMethionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III activity and MAT1A expression are compromised under pathological conditions such as alcoholic liver disease and hepatic cirrhosis, and this gene is silenced upon neoplastic transformation of the liver. In the present work, we evaluated whether MAT1A expression could be targeted by the polycyclic arylhydrocarbon (PAH) 3-methylcholanthrene (3-MC) in rat liver and cultured hepatocytes. MAT1A mRNA levels were reduced by 50% following in vivo administration of 3-MC to adult male rats (100 mg/kg, p.o., 4 days' treatment). This effect was reproduced in a time- and dose-dependent fashion in cultured rat hepatocytes, and was accompanied by the induction of cytochrome P450 1A1 gene expression. This action of 3-MC was mimicked by other PAHs such as benzo[a]pyrene and benzo[e]pyrene, but not by the model arylhydrocarbon receptor (AhR) activator 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3-MC inhibited transcription driven by a MAT1A promoter-reporter construct transfected into rat hepatocytes, but MAT1A mRNA stability was not affected. We recently showed that liver MAT1A expression is induced by AdoMet in cultured hepatocytes. Here, we observed that exogenously added AdoMet prevented the negative effects of 3-MC on MAT1A expression. Taken together, our data demonstrate that liver MAT1A gene expression is targeted by PAHs, independently of AhR activation. The effect of AdoMet may be part of the protective action of this molecule in liver damage.ElsevierDadun. Depósito Académico Digital Universidad de Navarra20122012-03-2820012001-01-0120012001-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21383reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/213832026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| title |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| spellingShingle |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine Carretero, M.V. (M. Victoria)|||/items/32989e88-e020-4ae5-befe-dcd0b529664b Liver damage Methionine metabolism Polycyclic aromatic hydrocarbons S-adenosylmethionine Methionine adenosyltransferase |
| title_short |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| title_full |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| title_fullStr |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| title_full_unstemmed |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| title_sort |
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine |
| dc.creator.none.fl_str_mv |
Carretero, M.V. (M. Victoria)|||/items/32989e88-e020-4ae5-befe-dcd0b529664b Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Ruiz Garcia-Trevijano, E. (Elena)|||/items/bc37b3f6-83de-42b9-bb68-e90d1296c35c Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2 Wagner, C. (Conrad)|||/items/62a28aa8-a141-407d-a9f5-1e3427145bb1 Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f |
| author |
Carretero, M.V. (M. Victoria)|||/items/32989e88-e020-4ae5-befe-dcd0b529664b |
| author_facet |
Carretero, M.V. (M. Victoria)|||/items/32989e88-e020-4ae5-befe-dcd0b529664b Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Ruiz Garcia-Trevijano, E. (Elena)|||/items/bc37b3f6-83de-42b9-bb68-e90d1296c35c Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2 Wagner, C. (Conrad)|||/items/62a28aa8-a141-407d-a9f5-1e3427145bb1 Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f |
| author_role |
author |
| author2 |
Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Ruiz Garcia-Trevijano, E. (Elena)|||/items/bc37b3f6-83de-42b9-bb68-e90d1296c35c Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2 Wagner, C. (Conrad)|||/items/62a28aa8-a141-407d-a9f5-1e3427145bb1 Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Liver damage Methionine metabolism Polycyclic aromatic hydrocarbons S-adenosylmethionine Methionine adenosyltransferase |
| topic |
Liver damage Methionine metabolism Polycyclic aromatic hydrocarbons S-adenosylmethionine Methionine adenosyltransferase |
| description |
Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III activity and MAT1A expression are compromised under pathological conditions such as alcoholic liver disease and hepatic cirrhosis, and this gene is silenced upon neoplastic transformation of the liver. In the present work, we evaluated whether MAT1A expression could be targeted by the polycyclic arylhydrocarbon (PAH) 3-methylcholanthrene (3-MC) in rat liver and cultured hepatocytes. MAT1A mRNA levels were reduced by 50% following in vivo administration of 3-MC to adult male rats (100 mg/kg, p.o., 4 days' treatment). This effect was reproduced in a time- and dose-dependent fashion in cultured rat hepatocytes, and was accompanied by the induction of cytochrome P450 1A1 gene expression. This action of 3-MC was mimicked by other PAHs such as benzo[a]pyrene and benzo[e]pyrene, but not by the model arylhydrocarbon receptor (AhR) activator 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3-MC inhibited transcription driven by a MAT1A promoter-reporter construct transfected into rat hepatocytes, but MAT1A mRNA stability was not affected. We recently showed that liver MAT1A expression is induced by AdoMet in cultured hepatocytes. Here, we observed that exogenously added AdoMet prevented the negative effects of 3-MC on MAT1A expression. Taken together, our data demonstrate that liver MAT1A gene expression is targeted by PAHs, independently of AhR activation. The effect of AdoMet may be part of the protective action of this molecule in liver damage. |
| publishDate |
2001 |
| dc.date.none.fl_str_mv |
2001 2001-01-01 2001 2001-01-01 2012 2012-03-28 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/21383 |
| url |
https://hdl.handle.net/10171/21383 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869416920331059200 |
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15,301603 |