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001-es BibID:	BIBFORM096063
035-os BibID:	(WoS)000655229800001 (Scopus)85106641226
Első szerző:	Batta Gyula (biológus)
Cím:	Statin-boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential / Gyula Batta, Levente Karpati, Gabriela Fulaneto Henrique, Gabriella Toth, Szabolcs Tarapcsak, Tamas Kovacs, Florina Zakany, Istvan M. Mandity, Peter Nagy
Dátum:	2021
ISSN:	0007-1188
Megjegyzések:	Background and purpose: Cell penetrating peptides are promising tools for delivery of cargo into cells, but factors limiting or facilitating their cellular uptake are largely unknown. We set out to study the effect of the biophysical properties of the cell membrane on the uptake of penetratin, a cell penetrating peptide. Experimental approach: Using labeling with pH-insensitive and pH-sensitive dyes, the kinetics of cellular uptake and endo-lysosomal escape of penetratin were studied by flow cytometry. Key results: We report that escape of penetratin from acidic endo-lysosomal compartments is retarded compared to its total cellular uptake. The membrane dipole potential, known to alter transmembrane transport of charged molecules, is shown to be negatively correlated with the concentration of penetratin in the cytoplasmic compartment. Treatment of cells with therapeutically relevant concentrations of atorvastatin, an inhibitor of HMG-CoA reductase and cholesterol synthesis, significantly increased endosomal escape of penetratin in two different cell types. This effect of atorvastatin correlated with its ability to decrease the membrane dipole potential. Conclusions and implications: These results highlight the importance of the dipole potential in regulating cellular uptake of cell penetrating peptides and suggest a clinically relevant way of boosting this process.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	British Journal Of Pharmacology. - 178 : 18 (2021), p. 3667-3681. -
További szerzők:	Kárpáti Levente (1968-) (okleveles vegyész) Henrique, Gabriela Fulaneto Tóth Gabriella Tarapcsák Szabolcs (1989-) (Molekuláris biológus) Kovács Tamás (1985-) (általános orvos) Zákány Florina (1989-) (általános orvos) Mándity István M. Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:	2018-1.2.1-NKP Egyéb GINOP-2.3.2-15-2016-00020 GINOP GINOP-2.3.2-15-2016-00044 GINOP K120302 OTKA ANN133421 Egyéb
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001-es BibID:	BIBFORM110635
035-os BibID:	(WoS)000985072100001 (Scopus)85151447550
Első szerző:	Kovács Tamás (általános orvos)
Cím:	Veklury (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content / Kovacs Tamas, Kurtan Kitti, Varga Zoltan, Nagy Peter, Panyi Gyorgy, Zakany Florina
Dátum:	2023
ISSN:	0007-1188
Megjegyzések:	Background and Purpose: Despite its contradictory clinical performance, remdesivir (Veklury®) has a pivotal role in COVID-19 therapy. Possible contributions of the vehicle, sulfobutylether-β-cyclodextrin (SBECD) to Veklury® effects have been overlooked. The powder and solution formulations of Veklury® are treated equivalently despite their different vehicle content. Our objective was to study Veklury® effects on initial membrane-coupled events of SARS-CoV-2 infection focusing on the cholesterol depletion-mediated role of SBECD. Experimental Approach: Using time-correlated flow cytometry and quantitative three-dimensional confocal microscopy, we studied early molecular events of SARS-CoV-2?host cell membrane interactions. Key Results: Veklury® and different cholesterol-depleting cyclodextrins (CDs) reduced binding of the spike receptor-binding domain (RBD) to ACE2 and spike trimer internalization for Wuhan-Hu-1, Delta and Omicron variants. Correlations of these effects with cholesterol-dependent changes in membrane structure and decreased lipid raft-dependent ACE2-TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector along with remdesivir due to its cholesteroldepleting potential. Veklury® solution inhibited RBD binding more efficiently due to its twice higher SBECD content. The CD-induced inhibitory effects were more prominent at lower RBD concentrations and in cells with lower endogenous ACE2 expression, indicating that the supportive CD actions can be even more pronounced during in vivo infection when viral load and ACE expression are typically low. Conclusion and Implications: Our findings call for the differentiation of Veklury® formulations in meta-analyses of clinical trials, potentially revealing neglected benefits of the solution formulation, and also raise the possibility of adjuvant cyclodextrin (CD) therapy, even at higher doses, in COVID-19.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk cholesterol cyclodextrin remdesivir SARS-CoV-2 spike glycoprotein
Megjelenés:	British Journal Of Pharmacology. - 180 : 16 (2023), p. 2064-2084. -
További szerzők:	Kurtán Kitti Varga Zoltán (1969-) (biofizikus, szakfordító) Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:	ANN133421 OTKA OTKA FK143400 OTKA K132906 OTKA K138075 OTKA K143071 OTKA UNKP-21-4-II-DE- 137 Egyéb UNKP-21-4-II-DE-138 Egyéb EFOP-3.6.2-16-2017-00006 Egyéb GINOP-2.3.2-15-2016-00015 Egyéb UNKP-22-4-II-DE-69 Egyéb
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