Source:http://linkedlifedata.com/resource/pubmed/id/17076759
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2007-1-23
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| 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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fura-2,
http://linkedlifedata.com/resource/pubmed/chemical/Prealbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0022-3042
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
100
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
446-57
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| 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.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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