Portal de investigación
Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine beta-synthase
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Rius-Pérez S
- Pérez S
- Martí-Andrés P
- Taléns-Visconti R
- Paradela A
- Guerrero L
- Franco L
- López-Rodas G
- Torres L
- Corrales F
- Sastre J
Grupos
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 2213-2317, 2213-2317
- Tipo:
- Article
- Páginas:
- 101324-101324
- PubMed:
- 31539805
- Factor de Impacto:
- 2,059 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Redox Biology ELSEVIER SCIENCE BV
Citas Recibidas en Web of Science: 22
Documentos
- No hay documentos
Filiaciones
Keywords
- Acute inflammation; S-adenosylmethionine; Homocysteine; Cystathionine beta-synthase; Nitrosative stress
Cita
Rius S,Pérez S,TORRES I,Martí P,Taléns R,Paradela A,Guerrero L,Franco L,López G,Torres L,Corrales F,Sastre J. Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine beta-synthase. Redox Biol. 2020. 28. p. 101324-101324. IF:11,799. (1).