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Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
J. Králová, M. Jurášek, L. Krčová, B. Dolenský, I. Novotný, M. Dušek, Z. Rottnerová, M. Kahle, P. Drašar, P. Bartůněk, V. Král,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
17-02836S
Grantová Agentura České Republiky (Grant Agency of the Czech Republic) - International
LO1220
Ministerstvo Školství, Mládeže a Tělovýchovy (Ministry of Education, Youth and Sports) - International
NLK
Directory of Open Access Journals
od 2011
Free Medical Journals
od 2011
Nature Open Access
od 2011-12-01
PubMed Central
od 2011
Europe PubMed Central
od 2011
ProQuest Central
od 2011-01-01
Open Access Digital Library
od 2011-01-01
Open Access Digital Library
od 2011-01-01
Health & Medicine (ProQuest)
od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2011
Springer Nature OA/Free Journals
od 2011-12-01
- MeSH
- biologický transport MeSH
- buněčná membrána chemie metabolismus MeSH
- buněčné linie MeSH
- cholesterol analýza metabolismus MeSH
- fluorescenční barviva chemie MeSH
- fluorescenční mikroskopie metody MeSH
- lidé MeSH
- lyzozomální nemoci z ukládání diagnóza metabolismus MeSH
- pyridiny chemie MeSH
- sloučeniny boru chemie MeSH
- steroly chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The monitoring of intracellular cholesterol homeostasis and trafficking is of great importance because their imbalance leads to many pathologies. Reliable tools for cholesterol detection are in demand. This study presents the design and synthesis of fluorescent probes for cholesterol recognition and demonstrates their selectivity by a variety of methods. The construction of dedicated library of 14 probes was based on heterocyclic (pyridine)-sterol derivatives with various attached fluorophores. The most promising probe, a P1-BODIPY conjugate FP-5, was analysed in detail and showed an intensive labelling of cellular membranes followed by intracellular redistribution into various cholesterol rich organelles and vesicles. FP-5 displayed a stronger signal, with faster kinetics, than the commercial TF-Chol probe. In addition, cells with pharmacologically disrupted cholesterol transport, or with a genetic mutation of cholesterol transporting protein NPC1, exhibited strong and fast FP-5 signal in the endo/lysosomal compartment, co-localizing with filipin staining of cholesterol. Hence, FP-5 has high potential as a new probe for monitoring cholesterol trafficking and its disorders.
Citace poskytuje Crossref.org
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