Linked Life Data

10751394

Source:http://linkedlifedata.com/resource/pubmed/id/10751394

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2000-7-20
pubmed:abstractText
Cholesterol accumulates to massive levels in cells from Niemann-Pick type C (NP-C) patients and in cells treated with class 2 amphiphiles that mimic NP-C disease. This behavior has been attributed to the failure of cholesterol released from ingested low density lipoproteins to exit the lysosomes. However, we now show that the rate of movement of cholesterol from lysosomes to plasma membranes in NP-C cells is at least as great as normal, as was also found previously for amphiphile-treated cells. Furthermore, the lysosomes in these cells filled with plasma membrane cholesterol in the absence of lipoproteins. In addition, we showed that the size of the endoplasmic reticulum cholesterol pool and the set point of the homeostatic sensor of cell cholesterol were approximately normal in NP-C cells. The plasma membrane cholesterol pools in both NP-C and amphiphile-treated cells were also normal. Furthermore, the build up of cholesterol in NP-C lysosomes was not a physiological response to cholesterol overload. Rather, it appeared that the accumulation in NP-C lysosomes results from an imbalance in the brisk flow of cholesterol among membrane compartments. In related experiments, we found that NP-C cells did not respond to class 2 amphiphiles (e.g. trifluoperazine, imipramine, and U18666A); these agents may therefore act directly on the NPC1 protein or on its pathway. Finally, we showed that the lysosomal cholesterol pool in NP-C cells was substantially and preferentially reduced by incubating cells with the oxysterols, 25-hydroxycholesterol and 7-ketocholesterol; these findings suggest a new pharmacological approach to the treatment of NP-C disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17468-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10751394-Androstenes, pubmed-meshheading:10751394-Anticholesteremic Agents, pubmed-meshheading:10751394-Cell Line, pubmed-meshheading:10751394-Cell Membrane, pubmed-meshheading:10751394-Cells, Cultured, pubmed-meshheading:10751394-Cholesterol, pubmed-meshheading:10751394-Culture Media, pubmed-meshheading:10751394-Endoplasmic Reticulum, pubmed-meshheading:10751394-Fibroblasts, pubmed-meshheading:10751394-Homeostasis, pubmed-meshheading:10751394-Humans, pubmed-meshheading:10751394-Imipramine, pubmed-meshheading:10751394-Kinetics, pubmed-meshheading:10751394-Lipoproteins, pubmed-meshheading:10751394-Lysosomes, pubmed-meshheading:10751394-Membrane Lipids, pubmed-meshheading:10751394-Monensin, pubmed-meshheading:10751394-Niemann-Pick Diseases, pubmed-meshheading:10751394-Skin, pubmed-meshheading:10751394-Trifluoperazine
pubmed:year
2000
pubmed:articleTitle
Cholesterol movement in Niemann-Pick type C cells and in cells treated with amphiphiles.
pubmed:affiliation
Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center University of Chicago, Chicago, Illinois 60637, USA. ylange@rush.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't