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Abstract: SA-PO720

Alanyl-Glutamine in Peritoneal Dialysis Fluids Restores Cytoprotective Responses of Endothelial Cells

Session Information

  • Peritoneal Dialysis - II
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis

Authors

  • Kratochwill, Klaus, Medical University of Vienna, Vienna, Austria
  • Tarantino, Silvia, Medical University of Vienna, Vienna, Austria
  • Herzog, Rebecca, Medical University of Vienna, Vienna, Austria
  • Bartosova, Maria, University of Heidelberg, Heidelberg, Germany
  • Schmitt, Claus P., University of Heidelberg, Heidelberg, Germany
  • Aufricht, Christoph, Medical University of Vienna, Vienna, Austria
Background

Peritoneal vascular changes manifested as vasculopathy and increased angiogenesis are major factors causing ultrafiltration failure in patients undergoing peritoneal dialysis (PD). Hyperglycemic conditions created during PD fluid (PDF) exposure are similar to those responsible for cellular pathomechanisms relevant in diabetic retinopathy and nephropathy. This study focused on characterizing endothelial cell (EC) injury and stress responses after exposure to PDF with/without cytoprotective intervention with alanyl-glutamine dipeptide (AlaGln).

Methods

Human umbilical vein ECs (HUVECs) exposed to PDF were subjected to a combined proteomic and bioinformatics approach using 2D-DIGE and fluorescent cyanine dyes. Cellular injury was associated with a molecular landscape of a set of enriched biological processes that characterize PDF cytotoxicity and counteracting cellular repair processes. These include “glucose catabolic process”, “cell redox homeostasis”, “RNA metabolic process”, “protein folding”, “regulation of cell death”, and of “actin cytoskeleton reorganization”.

Results

Supplementation of PDF with AlaGln preserved EC viability and restored control levels of proteins in PDF perturbed processes, especially enhancing protein folding capacity and response to stress. The direct comparison revealed a set of 55 differentially abundant spots of which 58.2% were restored with AlaGln. In support to the findings in our model, cross-comparison with transcriptomic data obtained from human peritoneal biopsies from children on PD showed changes in 12 potential marker genes of PDF cytotoxicity, of which 5 genes were restored to control levels following addition of AlaGln to the PD fluid.

Conclusion

This combined proteomics and bioinformatics approach shows that PDF harms endothelial cells and leads to drastic changes of the cellular process landscape. Cell damage and proteome changes were effectively counteracted by AlaGln. In summary, this study elucidates potential mechanisms by which AlaGln exerts cytoprotective effects in endothelial cells, offering therapeutic targets to reduce side effects of PD.