Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications
MTAP (5'-methylthioadenosine phosphorylase) catalyses the reversible phosphorolytic cleavage of methylthioadenosine leading to the production of methylthioribose-1-phosphate and adenine. Deficient MTAP activity has been correlated with human diseases including cirrhosis and hepatocellular carci...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2008 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/21417 |
| Acceso en línea: | https://hdl.handle.net/10171/21417 |
| Access Level: | acceso abierto |
| Palabra clave: | Cysteine oxidation, Inflammatio Methylthioadenosine Methylthioadenosine phosphorylase Oxidative stress Sulfenic acid |
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Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implicationsFernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718dSantamaria, M. (Mónica)|||/items/072812e5-8222-4bfc-96cd-c78ee9d883e3Sanchez-Quiles, V. (Virginia)|||/items/9e99781c-bce3-459d-a1d9-c08700f11905Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8Muñoz, J. (Javier)|||/items/a5dea34b-9970-44b5-a405-4031315a288fSanchez-del-Pino, M.M. (Manuel M.)|||/items/ebbc885a-5036-4bc0-b697-16ada2926964Valero, M.L. (María L.)|||/items/c3c591d8-b983-4945-a27e-56cd23813d70Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419fCorrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2Cysteine oxidation,InflammatioMethylthioadenosineMethylthioadenosine phosphorylaseOxidative stressSulfenic acidMTAP (5'-methylthioadenosine phosphorylase) catalyses the reversible phosphorolytic cleavage of methylthioadenosine leading to the production of methylthioribose-1-phosphate and adenine. Deficient MTAP activity has been correlated with human diseases including cirrhosis and hepatocellular carcinoma. In the present study we have investigated the regulation of MTAP by ROS (reactive oxygen species). The results of the present study support the inactivation of MTAP in the liver of bacterial LPS (lipopolysaccharide)-challenged mice as well as in HepG2 cells after exposure to t-butyl hydroperoxide. Reversible inactivation of purified MTAP by hydrogen peroxide results from a reduction of V(max) and involves the specific oxidation of Cys(136) and Cys(223) thiols to sulfenic acid that may be further stabilized to sulfenyl amide intermediates. Additionally, we found that Cys(145) and Cys(211) were disulfide bonded upon hydrogen peroxide exposure. However, this modification is not relevant to the mediation of the loss of MTAP activity as assessed by site-directed mutagenesis. Regulation of MTAP by ROS might participate in the redox regulation of the methionine catabolic pathway in the liver. Reduced MTA (5'-deoxy-5'-methylthioadenosine)-degrading activity may compensate for the deficient production of the precursor S-adenosylmethionine, allowing maintenance of intracellular MTA levels that may be critical to ensure cellular adaptation to physiopathological conditions such as inflammation.Portland PressDadun. Depósito Académico Digital Universidad de Navarra20122012-03-2920082008-01-0120082008-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21417reponame: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:10171/214172026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| title |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| spellingShingle |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d Cysteine oxidation, Inflammatio Methylthioadenosine Methylthioadenosine phosphorylase Oxidative stress Sulfenic acid |
| title_short |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| title_full |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| title_fullStr |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| title_full_unstemmed |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| title_sort |
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications |
| dc.creator.none.fl_str_mv |
Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d Santamaria, M. (Mónica)|||/items/072812e5-8222-4bfc-96cd-c78ee9d883e3 Sanchez-Quiles, V. (Virginia)|||/items/9e99781c-bce3-459d-a1d9-c08700f11905 Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8 Muñoz, J. (Javier)|||/items/a5dea34b-9970-44b5-a405-4031315a288f Sanchez-del-Pino, M.M. (Manuel M.)|||/items/ebbc885a-5036-4bc0-b697-16ada2926964 Valero, M.L. (María L.)|||/items/c3c591d8-b983-4945-a27e-56cd23813d70 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2 |
| author |
Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d |
| author_facet |
Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d Santamaria, M. (Mónica)|||/items/072812e5-8222-4bfc-96cd-c78ee9d883e3 Sanchez-Quiles, V. (Virginia)|||/items/9e99781c-bce3-459d-a1d9-c08700f11905 Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8 Muñoz, J. (Javier)|||/items/a5dea34b-9970-44b5-a405-4031315a288f Sanchez-del-Pino, M.M. (Manuel M.)|||/items/ebbc885a-5036-4bc0-b697-16ada2926964 Valero, M.L. (María L.)|||/items/c3c591d8-b983-4945-a27e-56cd23813d70 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2 |
| author_role |
author |
| author2 |
Santamaria, M. (Mónica)|||/items/072812e5-8222-4bfc-96cd-c78ee9d883e3 Sanchez-Quiles, V. (Virginia)|||/items/9e99781c-bce3-459d-a1d9-c08700f11905 Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8 Muñoz, J. (Javier)|||/items/a5dea34b-9970-44b5-a405-4031315a288f Sanchez-del-Pino, M.M. (Manuel M.)|||/items/ebbc885a-5036-4bc0-b697-16ada2926964 Valero, M.L. (María L.)|||/items/c3c591d8-b983-4945-a27e-56cd23813d70 Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2 |
| author2_role |
author author author author 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 |
Cysteine oxidation, Inflammatio Methylthioadenosine Methylthioadenosine phosphorylase Oxidative stress Sulfenic acid |
| topic |
Cysteine oxidation, Inflammatio Methylthioadenosine Methylthioadenosine phosphorylase Oxidative stress Sulfenic acid |
| description |
MTAP (5'-methylthioadenosine phosphorylase) catalyses the reversible phosphorolytic cleavage of methylthioadenosine leading to the production of methylthioribose-1-phosphate and adenine. Deficient MTAP activity has been correlated with human diseases including cirrhosis and hepatocellular carcinoma. In the present study we have investigated the regulation of MTAP by ROS (reactive oxygen species). The results of the present study support the inactivation of MTAP in the liver of bacterial LPS (lipopolysaccharide)-challenged mice as well as in HepG2 cells after exposure to t-butyl hydroperoxide. Reversible inactivation of purified MTAP by hydrogen peroxide results from a reduction of V(max) and involves the specific oxidation of Cys(136) and Cys(223) thiols to sulfenic acid that may be further stabilized to sulfenyl amide intermediates. Additionally, we found that Cys(145) and Cys(211) were disulfide bonded upon hydrogen peroxide exposure. However, this modification is not relevant to the mediation of the loss of MTAP activity as assessed by site-directed mutagenesis. Regulation of MTAP by ROS might participate in the redox regulation of the methionine catabolic pathway in the liver. Reduced MTA (5'-deoxy-5'-methylthioadenosine)-degrading activity may compensate for the deficient production of the precursor S-adenosylmethionine, allowing maintenance of intracellular MTA levels that may be critical to ensure cellular adaptation to physiopathological conditions such as inflammation. |
| publishDate |
2008 |
| dc.date.none.fl_str_mv |
2008 2008-01-01 2008 2008-01-01 2012 2012-03-29 |
| 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/10171/21417 |
| url |
https://hdl.handle.net/10171/21417 |
| 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 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Portland Press |
| publisher.none.fl_str_mv |
Portland Press |
| dc.source.none.fl_str_mv |
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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| repository.mail.fl_str_mv |
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1869406072061558784 |
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15,300719 |