Interleukin-1 and nerve growth factor induce hypersecretion and hypersulfation of neuroblastoma proteoglycans which bind beta-amyloid.
Inflammation and the response to injury may play an important role in the process of amyloidosis in Alzheimer's disease. We investigated the effect of interleukin-1 (IL-1) and nerve growth factor (NGF) on the metabolism of neuroblastoma proteoglycans. IL-1 and NGF increased the net charge and the net secretion of neuroblastoma proteoglycans. NGF also specifically increased the relative amount of cell-associated and secreted heparan sulfate proteoglycans in these cells. We previously demonstrated that neuroblastoma heparan sulfate proteoglycan binds specifically to the amyloid beta-amyloid peptide involved in Alzheimer's disease. Heparan sulfate glycosaminoglycans synthesized by IL-1-stimulated cells demonstrated an increased relative binding affinity for the beta-amyloid peptide. Thus, IL-1 and NGF induce the hypersecretion and hypersulfation of neuroblastoma heparan sulfate proteoglycans which bind beta-amyloid. These studies link the process of inflammation and repair with alterations in the metabolism of heparan sulfate proteoglycans and amyloid formation in Alzheimer's disease and other disorders.
Leveugle
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Henry L. Schwartz Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY 10029-6574, USA.
Ding
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Buée
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Fillit
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D016229:Amyloid beta-Peptides / Q000378:metabolism*; D004563:Electrochemistry; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D006025:Glycosaminoglycans; D007375:Interleukin-1; D009414:Nerve Growth Factors; D011509:Proteoglycans; D013431:Sulfates