Document Detail


Transthyretin Aggregates Induce Production of Reactive Nitrogen Species.
MedLine Citation:
PMID:  22627469     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background and Objective: Misfolded and aggregated transthyretins (agTTR) contribute to neurodegenerative amyloid diseases such as familial amyloid polyneuropathy and senile systemic amyloidosis. The neurotoxicity mechanisms of agTTR, however, are not well understood. In the current study, the possible contribution of reactive nitrogen species (RNS) to such mechanisms was investigated by examining agTTR-mediated changes in cellular RNS levels. Methods and Results: The production of RNS was assessed through nitrate and nitrite assays in two human cell lines after exposure to agTTR (2.4 μM pre-aggregation concentration). In both epidermoid (A431) and schwannoma (sNF94.3) cell lines, agTTR induced significant increases in RNS (p < 0.05 relative to the same concentration of normal TTR, or no-TTR controls). Redox modulators such as apocynin (1-(4-hydroxy-3-methoxy-phenyl)ethanone) and L-NMMA (N(G)-monomethyl-L-arginine) were tested for their effects on RNS production. These modulators decreased RNS production in both cell lines; although the effects of L-NMMA were statistically significant only in the schwannoma cells. Moreover, cells treated with agTTR exhibited decreases in metabolic activity relative to TTR- or non-TTR-treated cells (p < 0.05) as assessed by reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Conclusion: The results provide novel evidence for involvement of RNS in pro-oxidative effects of agTTR in two different human cell lines, and show that agTTR can induce more generalized changes in cellular metabolic activity.
Authors:
Vai-Hong Fong; Amandio Vieira
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-24
Journal Detail:
Title:  Neuro-degenerative diseases     Volume:  -     ISSN:  1660-2862     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101189034     Medline TA:  Neurodegener Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, B.C., Canada.
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