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Reactive oxygen species deglycosilate glomerular alpha-dystroglycan
N P J Vogtländer1, W P M Tamboer, M A H Bakker
1Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Kidney International
|May 5, 2006
Summary
Reactive oxygen species (ROS) damage glomerular alpha-dystroglycan (DG) glycosylation, disrupting podocyte structure and function in kidney disease. This deglycosylation impairs ligand binding and may cause podocyte detachment and foot process effacement.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Dystroglycan (DG) in podocytes is crucial for glomerular filtration barrier integrity.
- Alpha-dystroglycan (alpha-DG) glycosylation is vital for its function and negative charge.
- Reactive oxygen species (ROS) are implicated in glomerular diseases and can degrade carbohydrates.
Purpose of the Study:
- To investigate the impact of ROS on the glycosylation of glomerular alpha-DG.
- To determine how ROS-induced changes in alpha-DG affect its binding to ligands.
- To elucidate the role of ROS-mediated alpha-DG deglycosylation in kidney disease pathogenesis.
Main Methods:
- Utilized specific antibodies for core protein and glyco-epitopes of alpha-DG.
- Employed solid-phase assays, in situ kidney section analysis, and in vivo adriamycin nephropathy models.
- Performed ligand overlay assays to assess alpha-DG binding to laminin and agrin.
Main Results:
- Exposure to ROS caused a loss of carbohydrate epitopes on alpha-DG in vitro and in kidney sections.
- Deglycosylated alpha-DG exhibited reduced binding affinity to laminin and agrin.
- Adriamycin nephropathy model showed a significant loss of alpha-DG carbohydrate epitopes.
Conclusions:
- ROS-induced deglycosylation of glomerular alpha-DG disrupts the agrin-DG complex.
- This disruption may lead to podocyte detachment and foot process effacement in vivo.
- Impaired alpha-DG glycosylation by ROS contributes to glomerular disease progression.
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