PARK7 Diminishes Oxidative Stress-Induced Mucosal Damage in Celiac Disease
Joint Authors
Pap, Domonkos
Lippai, Rita
Szabó, Attila J.
Veres-Székely, Apor
Bernáth, Mária
Rokonay, Réka
Szebeni, Beáta
Takács, István M.
Vannay, Ádám
Cseh, Áron
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-09-07
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Coeliac disease (CD) is a chronic, immune-mediated small intestinal enteropathy, accompanied with gluten-triggered oxidative damage of duodenal mucosa.
Previously, our research group reported an increased mucosal level of the antioxidant protein Parkinson’s disease 7 (PARK7) in children with CD.
In the present study, we investigated the role of increased PARK7 level on the epithelial cell and mucosal integrity of the small intestine.
The presence of PARK7 was investigated using immunofluorescent staining on duodenal mucosa of children with CD and on FHs74Int duodenal epithelial cells.
To investigate the role of oxidative stress, FHs74Int cells were treated with H2O2 in the absence or presence of Comp23, a PARK7-binding compound.
Intracellular accumulation of reactive oxygen species (ROS) was determined by DCFDA-based assay.
Cell viability was measured by MTT, LDH, and Annexin V apoptosis assays.
Disruption of cytoskeleton and cell adhesion was investigated by immunofluorescence staining and by real-time RT PCR.
Effect of PARK7 on mucosal permeability was investigated ex vivo using intestinal sacs derived from control and Comp-23-pretreated mice.
Comp23 treatment reduced the H2O2-induced intracellular accumulation of ROS, thus preserving the integrity of the cytoskeleton and also the viability of the FHs74Int cells.
Accordingly, Comp23 treatment increased the expression of antioxidants (NRF2, TRX1, GCLC, HMOX1, NQO1), cell-cycle regulators (TP53, CDKN1A, PCNA, BCL2, BAX), and cell adhesion molecules (ZO1, CDH1, VCL, ITGB5) of H2O2-treated cells.
Pretreatment with Comp23 considerably decreased the small intestinal permeability.
In this study, we demonstrate that PARK7-binding Comp23 reduces the oxidative damage of duodenal epithelial cells, via increased expression of NRF2- and P53-regulated genes.
Our results suggest that PARK7 plays a significant role in the maintenance of mucosal integrity in CD.
American Psychological Association (APA)
Veres-Székely, Apor& Bernáth, Mária& Pap, Domonkos& Rokonay, Réka& Szebeni, Beáta& Takács, István M.…[et al.]. 2020. PARK7 Diminishes Oxidative Stress-Induced Mucosal Damage in Celiac Disease. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204615
Modern Language Association (MLA)
Veres-Székely, Apor…[et al.]. PARK7 Diminishes Oxidative Stress-Induced Mucosal Damage in Celiac Disease. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1204615
American Medical Association (AMA)
Veres-Székely, Apor& Bernáth, Mária& Pap, Domonkos& Rokonay, Réka& Szebeni, Beáta& Takács, István M.…[et al.]. PARK7 Diminishes Oxidative Stress-Induced Mucosal Damage in Celiac Disease. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204615
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204615