Document Detail

Interaction of the receptor for advanced glycation end products (RAGE) with transthyretin triggers nuclear transcription factor kB (NF-kB) activation.
MedLine Citation:
PMID:  10908156     Owner:  NLM     Status:  MEDLINE    
Mutated transthyretin (TTR) fibrils are associated with the pathology of familial amyloidotic polyneuropathy (FAP), in which extracellular amyloid deposits lead to degeneration of cells and tissues, in particular neurons of the peripheral nerve. Here we present evidence that the receptor for advanced glycation end products (RAGE), previously associated with Alzheimer's disease, acts as a selective cell surface acceptor site for both soluble and fibrillar TTR. Immunohistochemical studies demonstrating increased expression of RAGE in FAP tissues suggested the relevance of this receptor to TTR-induced fibrillar pathology. In vitro studies using soluble RAGE showed saturable specific interaction with soluble and fibrillar TTR with a K(d) of approximately 120 nM. However, no binding was observed when soluble TTR was combined with retinol-binding protein, which represents the form in which TTR normally circulates in plasma. Specific binding of TTR to RAGE-transfected Chinese hamster ovary cells (which was completely blocked by anti-RAGE) was observed, confirming that RAGE could mediate TTR binding to cellular surfaces. RAGE-dependent activation of nuclear transcription factor kB (NF-kB) by TTR fibrils was shown in PC-12 cells stably transfected to overexpress the receptor. Furthermore, FAP nerves showed up-regulation of p50, one of the NF-kB subunits, when compared with age-matched controls. From these observations we predict that, in vivo, the presence of TTR fibrils associated with cellular surfaces of FAP patients, by contributing to NF-kB activation, leads to the pathogenesis of neurodegeneration. Further insights into the consequences of the interaction of fibrillar TTR with RAGE may therefore provide a better understanding of neurodegeneration associated with FAP.
M M Sousa; S D Yan; D Stern; M J Saraiva
Related Documents :
3258066 - Androgens stimulate both growth rate and epidermal growth factor receptor activity of t...
2137326 - Changes associated with metastasis in b16-f1 melanoma cells surviving heat.
12488236 - Stimulation of gastrin-cckb receptor promotes migration of gastric ags cells via multip...
1847936 - An autocrine role for urokinase in phorbol ester-mediated differentiation of myeloid ce...
23820126 - Stronger antinociceptive efficacy of opioids at the injured nerve trunk than at its per...
19289926 - Blockade of glutamate transporters facilitates cerebellar synaptic long-term depression.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  80     ISSN:  0023-6837     ISO Abbreviation:  Lab. Invest.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-01     Completed Date:  2000-08-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1101-10     Citation Subset:  IM    
Amyloid Unit, Instituto de Biologia Molecular e Celular, Porto, Portugal.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
CHO Cells / metabolism
NF-kappa B / physiology*
PC12 Cells / metabolism
Prealbumin / metabolism,  physiology*
Receptors, Immunologic / metabolism,  physiology*
Reg. No./Substance:
0/NF-kappa B; 0/Prealbumin; 0/Receptors, Immunologic; 0/advanced glycosylation end-product receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Inhibition of monocyte chemotactic protein-1 synthesis by statins.
Next Document:  Autocrine growth regulation of CD30 ligand in CD30-expressing Reed-Sternberg cells: distinction betw...