Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-23
pubmed:abstractText
The deposition of transthyretin (TTR) amyloid in the PNS is a major pathological feature of familial amyloidotic polyneuropathy. The aim of the present study was to examine whether TTR could disrupt cytoplasmic Ca(2+) homeostasis and to determine the role of TTR aggregation in this process. The aggregation of amyloidogenic TTR was examined by solution turbidity, dynamic light scattering and atomic force microscopy. A nucleation-dependent polymerization process was observed in which TTR formed low molecular weight aggregates (oligomers < 100 nm in diameter) before the appearance of mature fibrils. TTR rapidly induced an increase in the concentration of intracellular Ca(2+) ([Ca(2+)](i)) when applied to SH-SY5Y human neuroblastoma cells. The greatest effect on [Ca(2+)](i) was induced by a preparation that contained the highest concentration of TTR oligomers. The TTR-induced increase in [Ca(2+)](i) was due to an influx of extracellular Ca(2+), mainly via L- and N-type voltage-gated calcium channels (VGCCs). These results suggest that increasing [Ca(2+)](i) via VGCCs may be an important early event which contributes to TTR-induced cytotoxicity, and that TTR oligomers, rather than mature fibrils, may be the major cytotoxic form of TTR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
446-57
pubmed:meshHeading
pubmed-meshheading:17076759-Calcium, pubmed-meshheading:17076759-Calcium Channel Blockers, pubmed-meshheading:17076759-Calcium Channels, pubmed-meshheading:17076759-Cell Line, Tumor, pubmed-meshheading:17076759-Dose-Response Relationship, Drug, pubmed-meshheading:17076759-Drug Interactions, pubmed-meshheading:17076759-Enzyme Inhibitors, pubmed-meshheading:17076759-Extracellular Fluid, pubmed-meshheading:17076759-Fura-2, pubmed-meshheading:17076759-Humans, pubmed-meshheading:17076759-Microscopy, Atomic Force, pubmed-meshheading:17076759-Mutation, pubmed-meshheading:17076759-Neuroblastoma, pubmed-meshheading:17076759-Prealbumin, pubmed-meshheading:17076759-Protein Structure, Quaternary, pubmed-meshheading:17076759-Thapsigargin, pubmed-meshheading:17076759-Time Factors, pubmed-meshheading:17076759-Transfection
pubmed:year
2007
pubmed:articleTitle
Transthyretin oligomers induce calcium influx via voltage-gated calcium channels.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't