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

0501282 - ÚMG 2019 RIV GB eng J - Článek v odborném periodiku
Králová, Jarmila - Jurasek, M. - Krcova, L. - Dolenský, B. - Novotný, Ivan - Dušek, Michal - Rottnerová, Z. - Kahle, Michal - Drasar, P. - Bartůněk, Petr - Král, V.
Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders.
Scientific Reports. Roč. 8, September (2018), č. článku 14428. ISSN 2045-2322. E-ISSN 2045-2322
Grant CEP: GA ČR GA17-02836S; GA MŠMT LO1220; GA MŠMT LM2015063; GA MŠMT(CZ) LM2015062; GA MŠMT LO1419; GA MŠMT(CZ) LO1603; GA MŠMT LM2011022
Institucionální podpora: RVO:68378271 ; RVO:68378050
Klíčová slova: intracellular cholesterol transport * niemann-pick-disease * plasma-membrane * bodipy-cholesterol * living cells * abiraterone acetate * fluorescent-probes * er * steatohepatitis * metabolism
Obor OECD: Organic chemistry; Condensed matter physics (including formerly solid state physics, supercond.) (FZU-D)
Impakt faktor: 4.011, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0293275