PhD Scientific Days 2019

Budapest, April 25–26, 2019

Protective role of PARK7 in celiac disease

Veres-Székely, Apor

Apor Veres-Székely1, Domonkos Pap2, Beáta Szebeni2, Zoltán Kiss2, István M. Takács1, András Arató1, Áron Cseh1, Attila Szabó1,2, Ádám Vannay1,2
1 1st Department of Pediatrics, Semmelweis University, Budapest
2 MTA-SE Pediatric and Nephrology Research Group

Language of the presentation

Hungarian

Text of the abstract

Introduction: 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 elevated mucosal level of PARK7 in children with CD.
Aims: In this study, we investigated the effect of PARK7 on the behavior of duodenal epithelial cells.
Method: Oxidative stress was induced by H2O2 treatment on FHs74Int duodenal epithelial cells in the absence or presence of Comp23, a PARK7 binding compound. Cell viability was measured by MTT and LDH assays. Accumulation of intracellular ROS was determined by DCFDA-based ROS assay. Gene expression changes were investigated by real-time RT PCR.
Results: Comp23 prevented epithelial cells against oxidative stress-induced cell death. While H2O2 resulted in increasing ROS accumulation in dose-dependent manner, co-treatment with Comp23 reduced intracellular oxidation. PARK7 activation induced the expression of antioxidants (NRF2, TRX1, GCLC, HMOX1, NQO1) and cell-cycle regulators (TP53, CDKN1A, PCNA, BCL2, BAX).
Conclusion: Our results showed, that PARK7 activation by Comp23 may reduce the consequence of oxidative damage via Nrf2 and p53 pathways in duodenal epithelial cells. PARK7 may play a significant role in the maintenance of mucosal integrity in CD.
Grant support: Supported by ÚNKP-18-3-I-SE-21, ÚNKP-18-4-SE-109 New National Excellence Program of the Ministry of Human Capacities, MTA-SE Pediatrics and Nephrology Research Group, Semmelweis Science and Innovation Fund., János Bolyai Research Scholarship of the Hungarian Academy of Sciences, FIKP 61822-64912 and OTKA K116928 grants.

Data of the presenter

Doctoral School: Clinical Medicine
Program: Prevention of Chronic Diseases in Childhood
Supervisor: Adam Vannay
E-mail address: veres-szekely.apor@med.semmelweis-univ.hu
oral presentation