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001-es BibID:BIBFORM097599
035-os BibID:(cikkazonosító)735357
Első szerző:Kovács Tamás (általános orvos)
Cím:Cyclodextrins exert a ligand-like current inhibitory effect on the KV1.3 ion channel independent of membrane cholesterol extraction / Tamas Kovacs, Tamas Sohajda, Lajos Szente, Peter Nagy, Gyorgy Panyi, Zoltan Varga, Florina Zakany
Dátum:2021
Megjegyzések:Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming water-soluble complexes with a variety of otherwise poorly soluble molecules including cholesterol and different drugs. Consistently, CDs are widely used in research and clinical practice to deplete cholesterol from cellular membranes or to increase solubility and bioavailability of different pharmaceuticals at local concentrations in the millimolar range. Effects of CDs exerted on cellular functions are generally thought to originate from reductions in cholesterol levels. Potential direct, ligand-like CD effects are largely neglected in spite of several recent studies reporting direct interaction between CDs and proteins including AMP activated protein kinase, ?-amyloid peptides, and ?-synuclein. In this study, by using patch-clamp technique, time-resolved quantitation of cholesterol levels and biophysical parameters and applying cholesterol-extracting and non-cholesterol-extracting CDs at 1 and 5 mM concentrations, we provide evidence for a previously unexplored ligand-like, cholesterol-independent current inhibitory effect of CDs on KV1.3, a prototypical voltage-gated potassium channel with pathophysiological relevance invarious autoimmune and neurodegenerative disorders. Our findings propose that potential direct CD effects on KV channels should be taken into consideration when interpreting functional consequences of CD treatments in both research and clinical practice. Furthermore, current-blocking effects of CDs on KV channels at therapeutically relevant concentrations might contribute to additional beneficial or adverse effects during their therapeutic applications.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
cyclodextrin
ligand-like interaction
membrane lipid order
membrane hydration
membrane fluidity
cholesterol
KV1.3
Megjelenés:Frontiers in Molecular Biosciences. - 8 (2021), p. 1-11. -
További szerzők:Sohajda Tamás Szente Lajos (1951-) (vegyész) Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Varga Zoltán (1969-) (biofizikus, szakfordító) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:UNKP-19-3-III-DE-92
Egyéb
UNKP-21-4-II-DE-138
Egyéb
UNKP-21-4-II-DE-137
Egyéb
NTP-NFTÖ-20-B-0115
Egyéb
EFOP-3.6.1-16-2016-00022
EFOP
GINOP-2.3.2-15-2016-00044
GINOP
OTKA K132906
OTKA
SNN139532
OTKA
K119417
OTKA
ANN133421
OTKA
2019-2.1.11-TÉT-2019-00059
Egyéb
2020-1.1.2-PIACI-KFI-2020-00092
Egyéb
Internet cím:DOI
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