Reactive oxygen species deglycosilate glomerular alpha-dystroglycan

Kidney Int. 2006 May;69(9):1526-34. doi: 10.1038/sj.ki.5000138.

Abstract

In the kidney, dystroglycan (DG) has been shown to cover the basolateral and apical membranes of the podocyte. alpha-DG is heavily glycosilated, which is important for its binding to laminin and agrin in the glomerular basement membrane. Furthermore, alpha-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 alpha-DG. By using specific antibodies directed against the core protein or glyco-epitopes of alpha-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 alpha-DG to its ligands. Exposure to ROS leads to a loss of carbohydrate epitopes on alpha-DG both in vitro and on kidney sections. In the in vitro assays, a decreased binding of deglycosilated alpha-DG to laminin and agrin was found. In adriamycin nephropathy, where radicals play a role, we observed a loss of alpha-DG carbohydrate epitopes. We conclude that deglycosilation of glomerular alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrin / analysis
  • Agrin / metabolism*
  • Animals
  • Cattle
  • Doxorubicin / toxicity
  • Dystroglycans / analysis
  • Dystroglycans / metabolism*
  • Glycosylation
  • Kidney Glomerulus / chemistry
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Laminin / analysis
  • Laminin / metabolism*
  • Muscle, Skeletal / chemistry
  • Podocytes / chemistry
  • Podocytes / drug effects
  • Podocytes / metabolism
  • Rabbits
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / etiology*
  • Renal Insufficiency / metabolism
  • Xanthine Oxidase / pharmacology

Substances

  • Agrin
  • Laminin
  • Reactive Oxygen Species
  • Dystroglycans
  • Doxorubicin
  • Xanthine Oxidase