Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders

Abstract 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 recogn...

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Autores principales:	Jarmila Králová, Michal Jurášek, Lucie Krčová, Bohumil Dolenský, Ivan Novotný, Michal Dušek, Zdeňka Rottnerová, Michal Kahle, Pavel Drašar, Petr Bartůněk, Vladimír Král
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Filipin Cholesterol Trafficking NPC Fibroblasts Dehydroergosterol (DHE) Abiraterone Acetate Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0647f34dfb5f4375bc68e664338d2298
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spelling	oai:doaj.org-article:0647f34dfb5f4375bc68e664338d22982021-12-02T15:07:45ZHeterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders10.1038/s41598-018-32776-62045-2322https://doaj.org/article/0647f34dfb5f4375bc68e664338d22982018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32776-6https://doaj.org/toc/2045-2322Abstract 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.Jarmila KrálováMichal JurášekLucie KrčováBohumil DolenskýIvan NovotnýMichal DušekZdeňka RottnerováMichal KahlePavel DrašarPetr BartůněkVladimír KrálNature PortfolioarticleFilipinCholesterol TraffickingNPC FibroblastsDehydroergosterol (DHE)Abiraterone AcetateMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Filipin Cholesterol Trafficking NPC Fibroblasts Dehydroergosterol (DHE) Abiraterone Acetate Medicine R Science Q
spellingShingle	Filipin Cholesterol Trafficking NPC Fibroblasts Dehydroergosterol (DHE) Abiraterone Acetate Medicine R Science Q Jarmila Králová Michal Jurášek Lucie Krčová Bohumil Dolenský Ivan Novotný Michal Dušek Zdeňka Rottnerová Michal Kahle Pavel Drašar Petr Bartůněk Vladimír Král Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
description	Abstract 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.
format	article
author	Jarmila Králová Michal Jurášek Lucie Krčová Bohumil Dolenský Ivan Novotný Michal Dušek Zdeňka Rottnerová Michal Kahle Pavel Drašar Petr Bartůněk Vladimír Král
author_facet	Jarmila Králová Michal Jurášek Lucie Krčová Bohumil Dolenský Ivan Novotný Michal Dušek Zdeňka Rottnerová Michal Kahle Pavel Drašar Petr Bartůněk Vladimír Král
author_sort	Jarmila Králová
title	Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
title_short	Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
title_full	Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
title_fullStr	Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
title_full_unstemmed	Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
title_sort	heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0647f34dfb5f4375bc68e664338d2298
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Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders

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