Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine beta-synthase
| Autor: | Rius-Pérez S, Pérez S, Torres-Cuevas I, Martí-Andrés P, Taléns-Visconti R, Paradela A, Guerrero L, Franco L, López-Rodas G, Torres L, Corrales F, Sastre J |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Redox Biology r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe |
| ISSN: | 2213-2317 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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