Evidence that glypican is a receptor mediating beta-amyloid neurotoxicity in PC12 cells.
Docking of beta-amyloid fibrils to neuronal or glial cell membranes may be an early, necessary and intervenable step during the progression of Alzheimer's disease. Formation of neurofibrillary tangles and amyloid plaques as well as neurotoxicity and inflammation may be direct or indirect consequences. In an attempt to find a receptor that mediates those effects, we assessed rat pheochromocytoma PC12 cell 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction after addition of beta-amyloid to the culture medium. Presence of competitive substances in the medium, cell-surface treatment and specific block of cellular synthesis pathways helped to identify the heparan sulphate moiety of a glycosylphosphatidylinositol-anchored protein likely to represent glypican as a possible receptor mediating beta-amyloid neurotoxicity.
Schulz
J G
JG
Department of Neurology, Charité Hospital, Humboldt-University, Berlin, Germany.
Megow
D
D
Reszka
R
R
Villringer
A
A
Einhäupl
K M
KM
Dirnagl
U
U
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006497:Heparan Sulfate / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D009994:Osmolar Concentration; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D009498:Neurotoxins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D013431:Sulfates