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1.

001-es BibID:BIBFORM087409
Első szerző:Hajdu Tímea (biomérnök)
Cím:Comprehensive Model for Epidermal Growth Factor Receptor Ligand Binding Involving Conformational States of the Extracellular and the Kinase Domains / Tímea Hajdu, Tímea Váradi, István Rebenku, Tamás Kovács, János Szöllösi, Péter Nagy
Dátum:2020
ISSN:2296-634X
Megjegyzések:The epidermal growth factor (EGF) receptor (EGFR) undergoes ligand-dependent dimerization to initiate transmembrane signaling. Although crystallographic structures of the extracellular and kinase domains are available, ligand binding has not been quantitatively analyzed taking the influence of both domains into account. Here, we developed a model explicitly accounting for conformational changes of the kinase and extracellular domains, their dimerizations and ligand binding to monomeric and dimeric receptor species. The model was fitted to ligand binding data of suspended cells expressing receptors with active or inactive kinase conformations. Receptor dimers with inactive, symmetric configuration of the kinase domains exhibit positive cooperativity and very weak binding affinity for the first ligand, whereas dimers with active, asymmetric kinase dimers are characterized by negative cooperativity and subnanomolar binding affinity for the first ligand. The homodimerization propensity of EGFR monomers with active kinase domains is _100-times higher than that of dimers with inactive kinase domains. Despite this fact, constitutive, ligand-independent dimers are mainly generated from monomers with inactive kinase domains due to the excess of such monomers in the membrane. The experimental finding of increased positive cooperativity at high expression levels of EGFR was recapitulated by the model. Quantitative prediction of ligand binding to different receptor species revealed that EGF binds to receptor monomers and dimers in an expression-level dependent manner without significant recruitment of monomers to dimers upon EGF stimulation below the phase transition temperature of the membrane. Results of the fitting offer unique insight into the workings of the EGFR.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
EGF
EGFR
Megjelenés:Frontiers in Cell and Developmental Biology. - 8 (2020), p. 1-53. -
További szerzők:Váradi Tímea (1973-) (biológus) Rebenku István Kovács Tamás (1985-) (általános orvos) Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00020
GINOP
GINOP-2.2.1-15-2017-00044
GINOP
NKFIH K120302
Egyéb
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM096387
035-os BibID:(cikkazonosító)737872
Első szerző:Shaw, Abhirup
Cím:Irisin stimulates the release of CXCL1 from differentiating human subcutaneous and deep-neck derived adipocytes via upregulation of NF[kappa]B pathway / Abhirup Shaw, Beáta B. Tóth, Róbert Király, Rini Arianti, István Csomós, Szilárd Póliska, Attila Vámos, Ilma R. Korponay-Szabó, Zsolt Bacso, Ferenc Győry, László Fésüs, Endre Kristóf
Dátum:2021
ISSN:2296-634X
Megjegyzések:Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed "batokines". Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines, CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 hours irisin treatment. Gene expression data indicated upregulation of the NF?B pathway upon irisin treatment, which was validated by an increase of p50 and decrease of I?B? protein level, respectively. Continuous blocking of the NF?B pathway, using a cell permeable inhibitor of NF?B nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NF?B pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Cell and Developmental Biology. - 9 (2021), p. 1-19. -
További szerzők:Bartáné Tóth Beáta (1970-) (molekuláris biológus) Király Róbert (1975-) (biológus) Arianti, Rini (1991-) (biokémikus) Csomós István (1983-) (molekuláris biológus) Póliska Szilárd (1978-) (biológus) Vámos Attila (1991-) (gyógyszer-biotechnológus) Korponay-Szabó Ilma (1959-) (gyermekgyógyász) Bacsó Zsolt (1963-) (biofizikus) Győry Ferenc (1964-) (sebész) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
FK131424
OTKA
K129139
OTKA
K120392
OTKA
ÚNKP-20-5-DE-12
Egyéb
BO/00042/18/8
MTA
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM116662
035-os BibID:(Scopus)85171172955 (WoS)001023372700001 (cikkazonosító)1249909
Első szerző:Vámos Attila (gyógyszer-biotechnológus)
Cím:Corrigendum : Human abdominal subcutaneous-derived active beige adipocytes carrying FTO rs1421085 obesity-risk alleles exert lower thermogenic capacity / Vámos Attila, Arianti Rini, Vinnai Boglárka Ágnes, Alrifai Rahaf, Shaw Abhirup, Póliska Szilárd, Guba Andrea, Csősz Éva, Csomós István, Mocsár Gábor, Lányi Cecilia, Balajthy Zoltán, Fésüs László, Kristóf Endre
Dátum:2023
ISSN:2296-634X
Megjegyzések:In the published article, there was an error. In the published article, the Reference "Bjune et al., 2005" was cited with an incorrect year of publication. The correct year of publication is 2019. In the published article "Bjune, J. I., Haugen, C., Gudbrandsen, O., Nordb?, O. P., Nielsen, H. J., V?age, V., et al. (2019). IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity. Int J Obes (Lond)., 43(11), 2151?2162. https://doi.org/10.1038/s41366-018-0275-y" was not referenced in the article. The reference has now been inserted into the article. A correction has been made to the Introduction. This sentence previously stated: "In addition, IRX5 silencing increased the mitochondrial respiration in isolated mouse adipocytes (Bjune et al., 2005)." The corrected sentence appears below: "In addition, IRX5 silencing increased the mitochondrial respiration in isolated mouse adipocytes (Bjune et al., 2019)." The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Copyright ? 2023 Vámos, Arianti, Vinnai, Alrifai, Shaw, Póliska, Guba, Csősz, Csomós, Mocsár, Lányi, Balajthy, Fésüs and Kristóf.
Tárgyszavak:Orvostudományok Elméleti orvostudományok hozzászólás
folyóiratcikk
adipocytes
beige
FTO rs1421085
obesity
SLC7A10
thermogenesis
UCP 1
Megjelenés:Frontiers in Cell and Developmental Biology. - 11 (2023), p. 1-2. -
További szerzők:Arianti, Rini (1991-) (biokémikus) Vinnai Boglárka Ágnes (1996-) (molekuláris biológus) Alrifai, Rahaf Shaw, Abhirup (1992-) Póliska Szilárd (1978-) (biológus) Guba Andrea (1975-) (Okleveles vegyész) Csősz Éva (1977-) (biokémikus, molekuláris biológus) Csomós István (1983-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Lányi Cecília Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM112108
035-os BibID:(cikkazonosító)1155673 (scopus)85164495947 (wos)001023372700001
Első szerző:Vámos Attila (gyógyszer-biotechnológus)
Cím:Human Abdominal Subcutaneous-Derived Active Beige Adipocytes Carrying FTO rs1421085 Obesity-Risk Alleles Exert Lower Thermogenic Capacity / Vámos Attila, Arianti Rini, Vinnai Boglárka Ágnes, Alrifai Rahaf, Shaw Abhirup, Póliska Szilárd, Guba Andrea, Csősz Éva, Csomós István, Mocsár Gábor, Lányi Cecília, Balajthy Zoltán, Fésüs László, Kristóf Endre
Dátum:2023
ISSN:2296-634X
Megjegyzések:White adipocytes store lipids, have a large lipid droplet and few mitochondria. Brown and beige adipocytes, which produce heat, are characterized by high expression of uncoupling protein (UCP) 1, multilocular lipid droplets, and large amounts of mitochondria. The rs1421085 T-to-C single-nucleotide polymorphism (SNP) of the human FTO gene interrupts a conserved motif for ARID5B repressor, resulting in adipocyte type shift from beige to white. We obtained abdominal subcutaneous adipose tissue from donors carrying FTO rs1421085 TT (risk-free) or CC (obesity-risk) genotypes, isolated and differentiated their preadipocytes into beige adipocytes (driven by the PPAR? agonist rosiglitazone for 14 days), and activated them with dibutyryl-cAMP for 4 hours. Then, either the same culture conditions were applied for additional 14 days (active beige adipocytes) or it was replaced by a white differentiation medium (inactive beige adipocytes). White adipocytes were differentiated by their medium for 28 days. RNA-sequencing was performed to investigate the gene expression pattern of adipocytes carrying different FTO alleles and found that active beige adipocytes had higher brown adipocyte content and browning capacity compared to white or inactive beige ones when the cells were obtained from risk-free TT but not from obesity-risk CC genotype carriers. Active beige adipocytes carrying FTO CC had lower thermogenic gene (e.g., UCP1, PM20D1, CIDEA) expression and thermogenesis measured by proton leak respiration as compared to TT carriers. In addition, active beige adipocytes with CC alleles exerted lower expression of ASC-1 neutral amino acid transporter (encoded by SLC7A10) and less consumption of Ala, Ser, Cys, and Gly as compared to risk-free carriers. We did not observe any influence of the FTO rs1421085 SNP on white and inactive beige adipocytes highlighting its exclusive and critical effect when adipocytes were activated for thermogenesis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adipocytes
beige
obesity
FTO rs1421085
thermogenesis
UCP1
SLC7A10
Megjelenés:Frontiers in Cell and Developmental Biology. - 11 (2023), p. 1-18. -
További szerzők:Arianti, Rini (1991-) (biokémikus) Vinnai Boglárka Ágnes (1996-) (molekuláris biológus) Alrifai, Rahaf Shaw, Abhirup (1992-) Póliska Szilárd (1978-) (biológus) Guba Andrea (1975-) (Okleveles vegyész) Csősz Éva (1977-) (biokémikus, molekuláris biológus) Csomós István (1983-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Lányi Cecília Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:FK131424
OTKA
K129139
OTKA
ÚNKP-22-3-I-DE-30
Egyéb
ÚNKP-22-3-II-DE-25
Egyéb
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

5.

001-es BibID:BIBFORM093476
035-os BibID:(cikkazonosító)647300
Első szerző:Zákány Florina (általános orvos)
Cím:An [omega]-3, but Not an [omega]-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin / Zakany Florina, Szabo Mate, Batta Gyula, Kárpáti Levente, Mándity István M., Fülöp Péter, Varga Zoltan, Panyi Gyorgy, Nagy Peter, Kovacs Tamas
Dátum:2021
ISSN:2296-634X 2296-634X
Megjegyzések:Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and &-6 g-linolenic acid (GLA) increase, while &-3 a-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity. Pretreatment with ALA counteracts, while SA or GLA enhances cholesterol-induced DP elevations. Furthermore, ALA (but not SA or GLA) increases endo-lysosomal escape of penetratin, a cell-penetrating peptide. In summary, we have developed a novel method to measure DP in large quantities of individual living cells and propose ALA as a physiological DP lowering agent facilitating cytoplasmic entry of penetratin.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
membrane dipole potential
polyunsaturated fatty acids
cholesterol
penetratin
flow cytometry
Megjelenés:Frontiers in Cell and Developmental Biology. - 9 (2021), p. 1-17. -
További szerzők:Szabó Máté Batta Gyula (1979-) (biológus) Kárpáti Levente (1968-) (okleveles vegyész) Mándity István M. Fülöp Péter (1974-) (belgyógyász, endokrinológus, lipidológus) Varga Zoltán (1969-) (biofizikus, szakfordító) Panyi György (1966-) (biofizikus) Nagy Péter (1971-) (biofizikus) Kovács Tamás (1985-) (általános orvos)
Pályázati támogatás:K120302
OTKA
ANN133421
OTKA
GINOP-2.3.2-15-2016-00020
GINOP
GINOP-2.3.2-15-2016-00044
GINOP
K132906
OTKA
TÉT - 2019 ? 2.1.11-TÉT-2019- 00059
Egyéb
K119417
OTKA
GINOP-2.3.2-15-2016-00015
GINOP
2018-1.2.1-NKP-2018-00005
Egyéb
UNKP-19-3-III-DE-92
Egyéb
NTP-NFTÖ-20-B-0115
Egyéb
MTA-DE Lendület
MTA
Matematikai és természettudományok - Kémiai tudományok
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Intézményi repozitóriumban (DEA) tárolt változat
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