Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine

Recent work shows that S-adenosylmethionine (AdoMet) helps maintain normal liver function as chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. The mechanisms by which these nontraditional functions of AdoMet occur are unknown. Here, we use...

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Detalhes bibliográficos
Autores: Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8, Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f, Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356, Rubio-Díaz-Cordovés, A. (Ángel)|||/items/7d740e1e-38db-46ea-9834-8c61aa6eedee, Martin-Duce, A. (Antonio)|||/items/38618fd4-155c-4043-97ec-35b500f9c390, Lu, S.C. (Shelly C.)|||/items/e4a2a6d5-e196-42c9-b95b-2a670ce9a801, Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79, Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
Formato: artículo
Fecha de publicación:2003
País:España
Recursos:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/21554
Acesso em linha:https://hdl.handle.net/10171/21554
Access Level:acceso abierto
Palavra-chave:Hepatitis/genetics
Hepatitis/metabolism
Mitochondrial Proteins/genetics
Mitochondrial Proteins/metabolism
Repressor Proteins
S-Adenosylmethionine/metabolism
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repository_id_str
spelling Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionineSantamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419fLatasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356Rubio-Díaz-Cordovés, A. (Ángel)|||/items/7d740e1e-38db-46ea-9834-8c61aa6eedeeMartin-Duce, A. (Antonio)|||/items/38618fd4-155c-4043-97ec-35b500f9c390Lu, S.C. (Shelly C.)|||/items/e4a2a6d5-e196-42c9-b95b-2a670ce9a801Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2Hepatitis/geneticsHepatitis/metabolismMitochondrial Proteins/geneticsMitochondrial Proteins/metabolismRepressor ProteinsS-Adenosylmethionine/metabolismRecent work shows that S-adenosylmethionine (AdoMet) helps maintain normal liver function as chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. The mechanisms by which these nontraditional functions of AdoMet occur are unknown. Here, we use knockout mice deficient in hepatic AdoMet synthesis (MAT1A(-/-)) to study the proteome of the liver during the development of steatohepatitis. One hundred and seventeen protein spots, differentially expressed during the development of steatohepatitis, were selected and identified by peptide mass fingerprinting. Among them, 12 proteins were found to be affected from birth, when MAT1A(-/-) expression is switched on in WT mouse liver, to the rise of histological lesions, which occurs at approximately 8 months. Of the 12 proteins, 4 [prohibitin 1 (PHB1), cytochrome c oxidase I and II, and ATPase beta-subunit] have known roles in mitochondrial function. We show that the alteration in expression of PHB1 correlates with a loss of mitochondrial function. Experiments in isolated rat hepatocytes indicate that AdoMet regulates PHB1 content, thus suggesting ways by which steatohepatitis may be induced. Importantly, we found the expression of these mitochondrial proteins was abnormal in obob mice and obese patients who are at risk for nonalcoholic steatohepatitis.National Academy of SciencesDadun. Depósito Académico Digital Universidad de Navarra20122012-04-0320032003-01-0120032003-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21554reponame: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:10171/215542026-06-21T12:47:57Z
dc.title.none.fl_str_mv Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
title Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
spellingShingle Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
Hepatitis/genetics
Hepatitis/metabolism
Mitochondrial Proteins/genetics
Mitochondrial Proteins/metabolism
Repressor Proteins
S-Adenosylmethionine/metabolism
title_short Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
title_full Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
title_fullStr Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
title_full_unstemmed Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
title_sort Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine
dc.creator.none.fl_str_mv Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356
Rubio-Díaz-Cordovés, A. (Ángel)|||/items/7d740e1e-38db-46ea-9834-8c61aa6eedee
Martin-Duce, A. (Antonio)|||/items/38618fd4-155c-4043-97ec-35b500f9c390
Lu, S.C. (Shelly C.)|||/items/e4a2a6d5-e196-42c9-b95b-2a670ce9a801
Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
author Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
author_facet Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8
Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356
Rubio-Díaz-Cordovés, A. (Ángel)|||/items/7d740e1e-38db-46ea-9834-8c61aa6eedee
Martin-Duce, A. (Antonio)|||/items/38618fd4-155c-4043-97ec-35b500f9c390
Lu, S.C. (Shelly C.)|||/items/e4a2a6d5-e196-42c9-b95b-2a670ce9a801
Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
author_role author
author2 Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356
Rubio-Díaz-Cordovés, A. (Ángel)|||/items/7d740e1e-38db-46ea-9834-8c61aa6eedee
Martin-Duce, A. (Antonio)|||/items/38618fd4-155c-4043-97ec-35b500f9c390
Lu, S.C. (Shelly C.)|||/items/e4a2a6d5-e196-42c9-b95b-2a670ce9a801
Mato, J.M. (José María)|||/items/302dc624-b0d3-4703-90cf-1a97690ebc79
Corrales, F.J. (Fernando José)|||/items/96b34843-1185-4837-be4b-d1d63e688ec2
author2_role 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 Hepatitis/genetics
Hepatitis/metabolism
Mitochondrial Proteins/genetics
Mitochondrial Proteins/metabolism
Repressor Proteins
S-Adenosylmethionine/metabolism
topic Hepatitis/genetics
Hepatitis/metabolism
Mitochondrial Proteins/genetics
Mitochondrial Proteins/metabolism
Repressor Proteins
S-Adenosylmethionine/metabolism
description Recent work shows that S-adenosylmethionine (AdoMet) helps maintain normal liver function as chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. The mechanisms by which these nontraditional functions of AdoMet occur are unknown. Here, we use knockout mice deficient in hepatic AdoMet synthesis (MAT1A(-/-)) to study the proteome of the liver during the development of steatohepatitis. One hundred and seventeen protein spots, differentially expressed during the development of steatohepatitis, were selected and identified by peptide mass fingerprinting. Among them, 12 proteins were found to be affected from birth, when MAT1A(-/-) expression is switched on in WT mouse liver, to the rise of histological lesions, which occurs at approximately 8 months. Of the 12 proteins, 4 [prohibitin 1 (PHB1), cytochrome c oxidase I and II, and ATPase beta-subunit] have known roles in mitochondrial function. We show that the alteration in expression of PHB1 correlates with a loss of mitochondrial function. Experiments in isolated rat hepatocytes indicate that AdoMet regulates PHB1 content, thus suggesting ways by which steatohepatitis may be induced. Importantly, we found the expression of these mitochondrial proteins was abnormal in obob mice and obese patients who are at risk for nonalcoholic steatohepatitis.
publishDate 2003
dc.date.none.fl_str_mv 2003
2003-01-01
2003
2003-01-01
2012
2012-04-03
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/10171/21554
url https://hdl.handle.net/10171/21554
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 National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.228081

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