Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/8/1178 |
| _version_ | 1827709985607385088 |
|---|---|
| author | Maria Bartosova Rebecca Herzog David Ridinger Eszter Levai Hanna Jenei Conghui Zhang Guadalupe T. González Mateo Iva Marinovic Thilo Hackert Felix Bestvater Michael Hausmann Manuel López Cabrera Klaus Kratochwill Sotirios G. Zarogiannis Claus Peter Schmitt |
| author_facet | Maria Bartosova Rebecca Herzog David Ridinger Eszter Levai Hanna Jenei Conghui Zhang Guadalupe T. González Mateo Iva Marinovic Thilo Hackert Felix Bestvater Michael Hausmann Manuel López Cabrera Klaus Kratochwill Sotirios G. Zarogiannis Claus Peter Schmitt |
| author_sort | Maria Bartosova |
| collection | DOAJ |
| description | Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane. |
| first_indexed | 2024-03-10T17:30:54Z |
| format | Article |
| id | doaj.art-ac83c647ff8d4fbf9d03cfbb2092dec1 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T17:30:54Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ac83c647ff8d4fbf9d03cfbb2092dec12023-11-20T10:02:34ZengMDPI AGBiomolecules2218-273X2020-08-01108117810.3390/biom10081178Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis FluidMaria Bartosova0Rebecca Herzog1David Ridinger2Eszter Levai3Hanna Jenei4Conghui Zhang5Guadalupe T. González Mateo6Iva Marinovic7Thilo Hackert8Felix Bestvater9Michael Hausmann10Manuel López Cabrera11Klaus Kratochwill12Sotirios G. Zarogiannis13Claus Peter Schmitt14Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyChristian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, AustriaKirchhoff Institute for Physics, Heidelberg University, 69120 Heidelberg, GermanyDivision of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyDivision of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyDivision of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyImmunology and Cellular Biology Department, Molecular Biology Centre Severo Ochoa, 28049 Madrid, SpainDivision of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyGeneral, Visceral and Transplantation Surgery, Heidelberg University, 69120 Heidelberg, GermanyGerman Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyKirchhoff Institute for Physics, Heidelberg University, 69120 Heidelberg, GermanyImmunology and Cellular Biology Department, Molecular Biology Centre Severo Ochoa, 28049 Madrid, SpainChristian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, AustriaDivision of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyDivision of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyUnderstanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.https://www.mdpi.com/2218-273X/10/8/1178peritoneal dialysistight junctionsparacellular transportalanyl-glutamine |
| spellingShingle | Maria Bartosova Rebecca Herzog David Ridinger Eszter Levai Hanna Jenei Conghui Zhang Guadalupe T. González Mateo Iva Marinovic Thilo Hackert Felix Bestvater Michael Hausmann Manuel López Cabrera Klaus Kratochwill Sotirios G. Zarogiannis Claus Peter Schmitt Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid Biomolecules peritoneal dialysis tight junctions paracellular transport alanyl-glutamine |
| title | Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid |
| title_full | Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid |
| title_fullStr | Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid |
| title_full_unstemmed | Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid |
| title_short | Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid |
| title_sort | alanyl glutamine restores tight junction organization after disruption by a conventional peritoneal dialysis fluid |
| topic | peritoneal dialysis tight junctions paracellular transport alanyl-glutamine |
| url | https://www.mdpi.com/2218-273X/10/8/1178 |
| work_keys_str_mv | AT mariabartosova alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT rebeccaherzog alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT davidridinger alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT eszterlevai alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT hannajenei alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT conghuizhang alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT guadalupetgonzalezmateo alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT ivamarinovic alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT thilohackert alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT felixbestvater alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT michaelhausmann alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT manuellopezcabrera alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT klauskratochwill alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT sotiriosgzarogiannis alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid AT clauspeterschmitt alanylglutaminerestorestightjunctionorganizationafterdisruptionbyaconventionalperitonealdialysisfluid |