Animal models; Electrophoresis; HSP70 Heat-Shock Proteins; Nephrology; Peritoneal Dialysis; Proteomics; Randomized Controlled Trial; Tandem Mass Spectrometry
Peritoneal dialysis (PD) is a life-saving renal replacement therapy for more than 200,000 patients worldwide. However, PD causes major morbidity and mortality due to infectious complications and peritoneal membrane failure. From a holistic view, this damage must be regarded as imbalance between PD-related cellular insults and counteracting stress responses.
Using a systems biology approach our previous work has obtained insight into intracellular events and functional pathways in models of experimental PD and thereby identified inadequate or suppressed cellular stress responses (CSR) in mesothelial cells exposed to PDF as a novel pathomechanism in PD. In our search for interventions for improving the CSR we identified the dipeptide alanyl-glutamine (Ala-Gln) as a promising cytoprotective additive to PDF. Current findings, so far, clearly support a specific role of Ala-Gln supplementation on the restoration of cytoprotective responses during PDF exposure, suggested by proteomic analysis of involved biological processes, which might be mediated by altered O-GlcNAcylation.
Techniques, methods & infrastructure
In our CDL we use omics techniques (transcriptomics, proteomics, metabolomics) to characterize molecular profiles of clinical samples and samples obtained from in-vitro and in-vivo models, using previously established bioinformatic tools as well as novel analytical approaches (high abundance protein depletion/low abundance protein enrichment approch, redox-proteomics, cross-omics comparison, etc.). Using orthogonal approaches (morphology, functional testing, testing in clinical trials) we aim to validate these molecular profiles.
- Christian Doppler Laboratory of Molecular Stress Research in Peritoneal Dialysis (CDL-MSRPD) (2016)
Source of Funding: CDG (Christian Doppler Research Association), Christian Doppler Labor
- Herzog, R. et al., 2017. Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid. Scientific Reports, 7(1). Available at: http://dx.doi.org/10.1038/s41598-017-05872-2.
- Kratochwill, K. et al., 2016. Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses - A First-In-Man Trial K. Eller, ed. PLOS ONE, 11(10), p.e0165045. Available at: http://dx.doi.org/10.1371/journal.pone.0165045.
- Herzog, R. et al., 2014. Dynamic O-Linked N-Acetylglucosamine Modification of Proteins Affects Stress Responses and Survival of Mesothelial Cells Exposed to Peritoneal Dialysis Fluids. Journal of the American Society of Nephrology, 25(12), pp.2778-2788. Available at: http://dx.doi.org/10.1681/ASN.2013101128.
- Rudashevskaya, E.L. et al., 2012. A method to resolve the composition of heterogeneous affinity-purified protein complexes assembled around a common protein by chemical cross-linking, gel electrophoresis and mass spectrometry. Nature Protocols, 8(1), pp.75-97. Available at: http://dx.doi.org/10.1038/nprot.2012.133.
- Kratochwill, K. et al., 2011. Alanyl-glutamine dipeptide restores the cytoprotective stress proteome of mesothelial cells exposed to peritoneal dialysis fluids. Nephrology Dialysis Transplantation, 27(3), pp.937-946. Available at: http://dx.doi.org/10.1093/ndt/gfr459.