Document Detail


Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes.
MedLine Citation:
PMID:  15810884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lipid rafts are cholesterol-enriched microdomains in plasma membranes. The functional activity of many membrane proteins, including death and growth factor receptors, depends on their insertion in lipid rafts. We have previously demonstrated the presence of lipid rafts in keratinocytes and shown that lipid rafts are involved in the control of keratinocyte proliferation and metabolic activity. In this work, we investigated the effect of lipid-raft disruption on HaCaT keratinocyte survival. Lipid rafts could be disrupted or rearranged with cholesterol-targeting detergents: methyl-beta-cyclodextrin and filipin III. Moreover, cholesterol oxidation by a specific oxidase or blocking of cholesterol synthesis by mevastatin had a similar effect on lipid rafts. All cholesterol-modifying substances caused cell death in a concentration-dependent manner. More detailed studies on the effects of cyclodextrin revealed apoptotic cell death at concentrations >or=0.5% (w/v). The molecular mechanism of apoptosis precipitated by raft disruption remains unknown but does not seem to be dependent of either membrane permeabilization or cell-cycle arrest imposed by cholesterol-modifying compounds.
Authors:
Bo Bang; Robert Gniadecki; Barbara Gajkowska
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Experimental dermatology     Volume:  14     ISSN:  0906-6705     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-06     Completed Date:  2005-07-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  266-72     Citation Subset:  IM    
Affiliation:
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. bb22@bbh.hosp.dk
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Cell Cycle
Cell Line, Tumor
Cell Membrane / metabolism
Cell Proliferation
Cholesterol / chemistry,  metabolism
Cholesterol Oxidase / metabolism
Detergents / pharmacology
Enzyme-Linked Immunosorbent Assay
Filipin / chemistry
Humans
In Situ Nick-End Labeling
Keratinocytes / cytology*
Lipids / chemistry*
Lovastatin / analogs & derivatives*,  chemistry
Membrane Microdomains / chemistry*
Microscopy, Confocal
Microscopy, Electron
Microscopy, Fluorescence
Time Factors
beta-Cyclodextrins / chemistry
Chemical
Reg. No./Substance:
0/Detergents; 0/Lipids; 0/beta-Cyclodextrins; 0/methyl-beta-cyclodextrin; 480-49-9/Filipin; 57-88-5/Cholesterol; 73573-88-3/compactin; 75330-75-5/Lovastatin; EC 1.1.3.6/Cholesterol Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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