Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis.

Abstract	Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand immunoglobulin superfamily cell surface molecule, is a receptor for the amyloidogenic form of serum amyloid A. Interactions between RAGE and amyloid A induced cellular perturbation. In a mouse model, amyloid A accumulation, evidence of cell stress and expression of RAGE were closely linked. Antagonizing RAGE suppressed cell stress and amyloid deposition in mouse spleens. These data indicate that RAGE is a potential target for inhibiting accumulation of amyloid A and for limiting cellular dysfunction induced by amyloid A.
Authors	S D Yan, H Zhu, A Zhu, A Golabek, H Du, A Roher, J Yu, C Soto, A M Schmidt, D Stern, M Kindy
Journal	Nature medicine (Nat Med) Vol. 6 Issue 6 Pg. 643-51 (Jun 2000) ISSN: 1078-8956 [Print] United States
PMID	10835680 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Amyloid Glycoproteins Interleukin-6 Islet Amyloid Polypeptide Membrane Proteins NF-kappa B Receptor for Advanced Glycation End Products Receptors, Immunologic Serum Amyloid A Protein amyloid enhancing factor Macrophage Colony-Stimulating Factor Silver Nitrate HMOX1 protein, human Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hmox1 protein, mouse
Topics	Amyloid (metabolism) Amyloidosis (metabolism, pathology) Animals Cell Line Glycoproteins (metabolism, pharmacology) Heme Oxygenase (Decyclizing) (genetics) Heme Oxygenase-1 Humans Interleukin-6 (genetics) Islet Amyloid Polypeptide Macrophage Colony-Stimulating Factor (genetics) Membrane Proteins Mice Mice, Inbred C57BL Monocytes (cytology, metabolism) NF-kappa B (metabolism) Rabbits Receptor for Advanced Glycation End Products Receptors, Immunologic (genetics, metabolism) Serum Amyloid A Protein (metabolism) Silver Nitrate (metabolism, pharmacology) Spleen (metabolism, pathology)

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