Linked Life Data

16884500

Source:http://linkedlifedata.com/resource/pubmed/id/16884500

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2006-8-3
pubmed:abstractText
Human amylin is a small fibrillogenic protein that is the major constituent of pancreatic islet amyloid, which occurs in most subjects with type 2 diabetes. There is evidence that it can elicit in vitro apoptosis in islet beta-cells, but the physical properties that underpin its cytotoxicity have not been clearly elucidated. Here we employed electron microscopy, thioflavin T fluorescence and CD spectroscopy to analyze amylin preparations whose cytotoxic potential was established by live-dead assay in cultured beta-cells. Highly toxic amylin contained few preformed fibrils and initially showed little beta-sheet content, but underwent marked time-dependent aggregation and beta-conformer formation following dissolution. By contrast, low-toxicity amylin contained abundant preformed fibrils, and demonstrated high initial beta-sheet content but little propensity to aggregate further once dissolved. Thus, mature amylin fibrils are not toxic to beta-cells, and aggregates of fibrils such as occur in pancreatic islet amyloid in vivo are unlikely to contribute to beta-cell loss. Rather, the toxic molecular species is likely to comprise soluble oligomers with significant beta-sheet content. Attempts to find ways of protecting beta-cells from amylin-mediated death might profitably focus on preventing the conformational change from random coil to beta-sheet.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1742-464X
pubmed:author
pubmed:issnType
Print
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3614-24
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The aggregation potential of human amylin determines its cytotoxicity towards islet beta-cells.
pubmed:affiliation
School of Biological Sciences, Faculty of Science, University of Auckland, New Zealand.
pubmed:publicationType
Journal Article