Disulfide stress: a novel type of oxidative stress in acute pancreatitis

Fecha de publicación: 01/05/2014

Autores de IIS La Fe

Justo Javier Escobar Cubiella

Autor
Máximo Vento Torres

Autor
Juan J. Sastre Belloch

Autor

Participantes ajenos a IIS La Fe

Moreno ML
Izquierdo-Álvarez A
Gil A
Pérez S
Pereda J
Zapico I
Sabater L
Marina A
Martínez-Ruiz A

Grupos

Perinatología

Leader

Máximo Vento Torres

Abstract

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and gamma-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis. Protein cysteinylation was undetectable in pancreas under basal conditions. Targets of disulfide stress were identified by Western blotting, diagonal electrophoresis, and proteomic methods. Cysteinylated albumin was detected. Redox-sensitive PP2A and tyrosine protein phosphatase activities diminished in pancreatitis and this loss was abrogated by N-acetylcysteine. According to our findings, disulfide stress may be considered a specific type of oxidative stress in acute inflammation associated with protein cysteinylation and gamma-glutamylcysteinylation and oxidation of the pair cysteine/cystine, but without glutathione oxidation or changes in protein glutathionylation. Two types of targets of disulfide stress were identified: redox buffers, such as ribonuclease inhibitor or albumin, and redox-signaling thiols, which include thioredoxin 1, APE1/Ref1, Keap1, tyrosine and serine/threonine phosphatases, and protein disulfide isomerase. These targets exhibit great relevance in DNA repair, cell proliferation, apoptosis, endoplasmic reticulum stress, and inflammatory response. Disulfide stress would be a specific mechanism of redox signaling independent of glutathione redox status involved in inflammation. (C) 2014 Elsevier Inc. All rights reserved.

Datos de la publicación

ISSN/ISSNe:: 0891-5849, 1873-4596
Tipo:: Article
Páginas:: 265-277
DOI:: 10.1016/j.freeradbiomed.2014.01.009
PubMed:: 24456905
Factor de Impacto:: 2,469 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Moreno ML:: Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot (Valencia), Spain
Escobar J:: Division of Neonatology, University Hospital Materno-Infantil La Fe, 46026 Valencia, Spain
Izquierdo-Álvarez A:: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
Gil A:: Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot (Valencia), Spain
Pérez S:: Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot (Valencia), Spain
Pereda J:: Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot (Valencia), Spain
Zapico I:: Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Madrid, Spain
Vento M:: Division of Neonatology, University Hospital Materno-Infantil La Fe, 46026 Valencia, Spain
Sabater L:: Department of Surgery, University Clinic Hospital, University of Valencia, 46010 Valencia, Spain
Marina A:: Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Madrid, Spain
Martínez-Ruiz A:: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
Sastre J:: Department of Physiology, School of Pharmacy, University of Valencia, 46100 Burjasot (Valencia), Spain.