Biophysical impact of sphingosine and other abnormal lipid accumulation in Niemann-Pick disease type C cell models

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>

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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Type

J_imp - 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

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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