02.05 Glutathione Peroxidase Two Expression is Upregulated in Necrotizing Enterocolitis

G. H. Gershner1,2, K. B. Snyder1,2, C. Calkins1,2, C. Dalton1,2, C. J. Hunter1,2  1Oklahoma Children’s Hospital, Division Of Pediatric Surgery, Oklahoma City, OK, USA 2The University of Oklahoma Health Sciences Center, Department Of Surgery, Oklahoma City, OK, USA

Introduction: Despite decades of research and advancement, NEC remains a devastating disease associated with high morbidity and mortality in the neonatal population. GPX enzymes are ubiquitous in the body and previous studies have shown a decrease in glutathione peroxidase 4 (GPX4) in patients with NEC. Those of interest include GPX1 (cytosolic) and GPX2 (intestinal, liver, gallbladder).  Our study examined gene expression of GPX1, GPX2, and glutathione synthetase. We hypothesize that these enzymes will have a decreased expression in NEC, leading to higher amounts of ROS and increased proclivity to NEC.

Methods: Intestinal tissue was collected from premature neonates with and without NEC already undergoing surgical resection. RNA was isolated from the tissue for analysis.  All patients were age-matched at the time of resection for experimentation. RTqPCR was performed to analyze GPX1, GPX2, and glutathione synthetase (GSS) gene expression.  ANOVA was performed for statistical analysis.

Results: Our results showed that GPX2 was significantly elevated across active NEC patients (p<0.01). GPX1 was significantly elevated in one NEC pt (p<0.005), and up-trending in the other.  GSS was marginally significant in one NEC patient (p≤0.05), but significantly decreased in another (0.0002).

Conclusion: Our study showed that GPX2 was significantly elevated in NEC, while GPX1 and GSS were inconsistent. Given a previous study showing that GPX4 had decreased activity in NEC, it appears that the elevation of GPX2 in NEC could be a response to oxidative stress.  While GPX2 mainly targets hydrogen peroxide, it is able to assist in other glutathione-based redox reactions. The inconsistent levels of GPX1 and GSS, and further clarification of GPX2 overexpression warrant further study.