Biophysical impact of sphingosine and other abnormal lipid accumulation in Niemann-Pick disease type C cell models
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F21%3A00542461" target="_blank" >RIV/61388955:_____/21:00542461 - isvavai.cz</a>
Result on the web
<a href="http://hdl.handle.net/11104/0319870" target="_blank" >http://hdl.handle.net/11104/0319870</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bbalip.2021.158944" target="_blank" >10.1016/j.bbalip.2021.158944</a>
Alternative languages
Result language
angličtina
Original language name
Biophysical impact of sphingosine and other abnormal lipid accumulation in Niemann-Pick disease type C cell models
Original language description
Niemann-Pick disease type C (NPC) is a complex and rare pathology, which is mainly associated to mutations in the NPC1 gene. This disease is phenotypically characterized by the abnormal accumulation of multiple lipid species in the acidic compartments of the cell. Due to the complexity of stored material, a clear molecular mechanism explaining NPC pathophysiology is still not established. Abnormal sphingosine accumulation was suggested as the primary factor involved in the development of NPC, followed by the accumulation of other lipid species. To provide additional mechanistic insight into the role of sphingosine in NPC development, fluorescence spectroscopy and microscopy were used to study the biophysical properties of biological membranes using different cellular models of NPC. Addition of sphingosine to healthy CHO-K1 cells, in conditions where other lipid species are not yet accumulated, caused a rapid decrease in plasma membrane and lysosome membrane fluidity, suggesting a direct effect of sphingosine rather than a downstream event. Changes in membrane fluidity caused by addition of sphingosine were partially sustained upon impaired trafficking and metabolization of cholesterol in these cells, and could recapitulate the decrease in membrane fluidity observed in NPC1 null Chinese Hamster Ovary (CHO) cells (CHO-M12) and in cells with pharmacologically induced NPC phenotype (treated with U18666A). In summary, these results show for the first time that the fluidity of the membranes is altered in models of NPC and that these changes are in part caused by sphingosine, supporting the role of this lipid in the pathophysiology of NPC.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids
ISSN
1388-1981
e-ISSN
1879-2618
Volume of the periodical
1866
Issue of the periodical within the volume
8
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
13
Pages from-to
158944
UT code for WoS article
000656122900004
EID of the result in the Scopus database
2-s2.0-85105045187