Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase

Acute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the...

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Authors: Rius-Perez, Sergio, Perez, Salvador, Torres-Cuevas, Isabel, Marti-Andres, Pablo, Talens-Visconti, Raquel, Paradela, Alberto, Guerrero, Laura, Franco, Luis, Lopez-Rodas, Gerardo, Torres, Luis, Corrales, Fernando, Sastre, Juan
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:INCLIVA
Repository:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p4022
Online Access:https://incliva.portalinvestigacion.com/publicaciones/4022
Access Level:Open access
Keyword:Acute inflammation
S-adenosylmethionine
Homocysteine
Cystathionine beta-synthase
Nitrosative stress
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spelling Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthaseRius-Perez, SergioPerez, SalvadorTorres-Cuevas, IsabelMarti-Andres, PabloTalens-Visconti, RaquelParadela, AlbertoGuerrero, LauraFranco, LuisLopez-Rodas, GerardoTorres, LuisCorrales, FernandoSastre, JuanAcute inflammationS-adenosylmethionineHomocysteineCystathionine beta-synthaseNitrosative stressAcute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the causes of this dysregulation in an experimental model of acute pancreatitis; and secondly to reveal the effects of S-adenosylmethionine administration on these pathways. Acute pancreatitis was induced by cerulein in mice, and a group of animals received S-adenosylmethionine treatment. Cerulein-induced acute pancreatitis rapidly caused marked depletion of methionine, S-adenosylmethionine, 5'-methylthioadenosine, cystathionine, cysteine, and glutathione levels in pancreas, but S-adenosylhomocysteine and homocysteine remained unchanged. Protein steady-state levels of S-adenosylhomocysteine-hydrolase and cystathionine gamma-lyase diminished but methylthioadenosine phosphorylase levels increased in pancreas with acute pancreatitis. Although cystathionine beta-synthase protein levels did not change with acute pancreatitis, Nos2 mRNA and protein levels were markedly up-regulated and caused tyrosine nitration of cystathionine beta-synthase in pancreas. S-adenosylmethionine administration enhanced Nos2 mRNA expression and cystathionine beta-synthase nitration and triggered homocysteine accumulation in acute pancreatitis. Furthermore, S-adenosylmethionine administration promoted enrichment of the euchromatin marker H3K4me3 in the promoters of Tnf-alpha, Il-6, and Nos2 and enhanced the mRNA up-regulation of these genes. Accordingly, S-adenosylmethionine administration increased inflammatory infiltrate and edema in pancreas with acute pancreatitis. In conclusion, tyrosine-nitration of cystathionine beta-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment. Copyright © 2019. Published by Elsevier B.V.ELSEVIER2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/4022Redox BiologyISSN: 22132317reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p40222026-06-07T16:35:31Z
dc.title.none.fl_str_mv Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
title Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
spellingShingle Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
Rius-Perez, Sergio
Acute inflammation
S-adenosylmethionine
Homocysteine
Cystathionine beta-synthase
Nitrosative stress
title_short Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
title_full Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
title_fullStr Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
title_full_unstemmed Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
title_sort Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine ß-synthase
dc.creator.none.fl_str_mv Rius-Perez, Sergio
Perez, Salvador
Torres-Cuevas, Isabel
Marti-Andres, Pablo
Talens-Visconti, Raquel
Paradela, Alberto
Guerrero, Laura
Franco, Luis
Lopez-Rodas, Gerardo
Torres, Luis
Corrales, Fernando
Sastre, Juan
author Rius-Perez, Sergio
author_facet Rius-Perez, Sergio
Perez, Salvador
Torres-Cuevas, Isabel
Marti-Andres, Pablo
Talens-Visconti, Raquel
Paradela, Alberto
Guerrero, Laura
Franco, Luis
Lopez-Rodas, Gerardo
Torres, Luis
Corrales, Fernando
Sastre, Juan
author_role author
author2 Perez, Salvador
Torres-Cuevas, Isabel
Marti-Andres, Pablo
Talens-Visconti, Raquel
Paradela, Alberto
Guerrero, Laura
Franco, Luis
Lopez-Rodas, Gerardo
Torres, Luis
Corrales, Fernando
Sastre, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Acute inflammation
S-adenosylmethionine
Homocysteine
Cystathionine beta-synthase
Nitrosative stress
topic Acute inflammation
S-adenosylmethionine
Homocysteine
Cystathionine beta-synthase
Nitrosative stress
description Acute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the causes of this dysregulation in an experimental model of acute pancreatitis; and secondly to reveal the effects of S-adenosylmethionine administration on these pathways. Acute pancreatitis was induced by cerulein in mice, and a group of animals received S-adenosylmethionine treatment. Cerulein-induced acute pancreatitis rapidly caused marked depletion of methionine, S-adenosylmethionine, 5'-methylthioadenosine, cystathionine, cysteine, and glutathione levels in pancreas, but S-adenosylhomocysteine and homocysteine remained unchanged. Protein steady-state levels of S-adenosylhomocysteine-hydrolase and cystathionine gamma-lyase diminished but methylthioadenosine phosphorylase levels increased in pancreas with acute pancreatitis. Although cystathionine beta-synthase protein levels did not change with acute pancreatitis, Nos2 mRNA and protein levels were markedly up-regulated and caused tyrosine nitration of cystathionine beta-synthase in pancreas. S-adenosylmethionine administration enhanced Nos2 mRNA expression and cystathionine beta-synthase nitration and triggered homocysteine accumulation in acute pancreatitis. Furthermore, S-adenosylmethionine administration promoted enrichment of the euchromatin marker H3K4me3 in the promoters of Tnf-alpha, Il-6, and Nos2 and enhanced the mRNA up-regulation of these genes. Accordingly, S-adenosylmethionine administration increased inflammatory infiltrate and edema in pancreas with acute pancreatitis. In conclusion, tyrosine-nitration of cystathionine beta-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment. Copyright © 2019. Published by Elsevier B.V.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/4022
url https://incliva.portalinvestigacion.com/publicaciones/4022
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv Redox Biology
ISSN: 22132317
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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