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

Redox Biology  ELSEVIER SCIENCE BV

Tipo:
Article
Páginas:
101324-101324
PubMed:
31539805
Factor de Impacto:
2,059 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 11

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Keywords

  • Acute inflammation; S-adenosylmethionine; Homocysteine; Cystathionine beta-synthase; Nitrosative stress

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