Journal article
Reactive oxygen species deglycosilate glomerular α-dystroglycan
Kidney international, Vol.69(9), pp.1526-1534
05/01/2006
DOI: 10.1038/sj.ki.5000138
PMID: 16672922
Abstract
In the kidney, dystroglycan (DG) has been shown to cover the basolateral and apical membranes of the podocyte. α-DG is heavily glycosilated, which is important for its binding to laminin and agrin in the glomerular basement membrane. Furthermore, α-DG is negatively charged, which maintains the filtration slit open. Reactive oxygen species (ROS) are known to degrade and depolymerize carbohydrates, and to play a role in several glomerular diseases. Therefore, we evaluated the effect of ROS on the glycosilation of glomerular α-DG. By using specific antibodies directed against the core protein or glyco-epitopes of α-DG, this was studied in a solid-phase assay, in situ on kidney sections, and in vivo in adriamycin nephropathy. A ligand overlay assay was used to study binding of α-DG to its ligands. Exposure to ROS leads to a loss of carbohydrate epitopes on α-DG both in vitro and on kidney sections. In the in vitro assays, a decreased binding of deglycosilated α-DG to laminin and agrin was found. In adriamycin nephropathy, where radicals play a role, we observed a loss of α-DG carbohydrate epitopes. We conclude that deglycosilation of glomerular α-DG by ROS leads to disruption of the agrin–DG complex, which in vivo may lead to the detachment of podocytes. Furthermore, loss of negative charge in the filtration slit may lead to foot process effacement of podocytes.
Details
- Title: Subtitle
- Reactive oxygen species deglycosilate glomerular α-dystroglycan
- Creators
- N.P.J Vogtländer - Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsW.P.M Tamboer - Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsM.A.H Bakker - Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsK.P Campbell - Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa, USAJ van der Vlag - Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsJ.H.M Berden - Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
- Resource Type
- Journal article
- Publication Details
- Kidney international, Vol.69(9), pp.1526-1534
- DOI
- 10.1038/sj.ki.5000138
- PMID
- 16672922
- NLM abbreviation
- Kidney Int
- ISSN
- 0085-2538
- eISSN
- 1523-1755
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/01/2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020869702771
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