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1.

001-es BibID:BIBFORM060614
Első szerző:Balajthy Zoltán (biokémikus, sejtbiológus)
Cím:Lack of induction of tissue transglutaminase but activation of the preexisting enzyme in c-myc-induced apoptosis of CHO Cells / Zoltán Balajthy, Noémi Kedei, László Nagy, Peter J. A. Davies, László Fésüs
Dátum:1997
ISSN:0006-291X
Megjegyzések:The intracellular activity and expression of tissue transglutaminase, which crosslinks proteins through ?(γ-glutamyl)lysine isodipeptide bond, was investigated in CHO cells and those stably transfected with either inducible c-Myc (which leads to apoptosis) or with c-myc and the apoptosis inhibitor Bcl-2. Protein-bound cross-link content was significantly higher when apoptosis was induced by c-Myc while the concomitant presence of Bcl-2 markedly reduced both apoptosis and enzymatic protein cross-linking. The expression of tissue transglutaminase did not change following the initiation of apoptosis by c-Myc or when it was blocked by Bcl-2. Studying transiently co-transfected elements of the mouse tissue transglutaminase promoter linked to a reporter enzyme revealed their overall repression in cells expressing c-Myc. This repression was partially suspended in cells also carrying Bcl-2. Our data suggest that tissue transglutaminase is not induced when c-Myc initiates apoptosis but the pre-existing endogenous enzyme is activated.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Biochemical and Biophysical Research Communications 236 : 2 (1997), p. 280-284. -
További szerzők:Kedei Noémi Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Davies, Peter J. A. Fésüs László (1947-) (orvos biokémikus)
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2.

001-es BibID:BIBFORM016665
Első szerző:Balajthy Zoltán (biokémikus, sejtbiológus)
Cím:Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions / Zoltán Balajthy, Krisztián Csomós, György Vámosi, Attila Szántó, Michel Lanotte, László Fésüs
Dátum:2006
ISSN:0006-4971
Megjegyzések:Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Blood. - 108 : 6 (2006), p. 2045-2054. -
További szerzők:Csomós Krisztián (1981-) (molekuláris biológus) Vámosi György (1967-) (biofizikus) Szántó Attila (1976-) (orvos, biokémikus) Lanotte, Michel Fésüs László (1947-) (orvos biokémikus)
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3.

001-es BibID:BIBFORM064340
035-os BibID:(WoS)000382077800015 (Scopus)85013262896
Első szerző:Csomós Krisztián (molekuláris biológus)
Cím:Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps / Krisztián Csomós, Endre Kristóf, Bernadett Jakob, István Csomós, György Kovács, Omri Rotem, Judit Hodrea, Zsuzsa Bagoly, Laszlo Muszbek, Zoltán Balajthy, Éva Csősz, László Fésüs
Dátum:2016
ISSN:2041-4889
Megjegyzések:Neutrophil extracellular trap (NET) ejected from activated dying neutrophils is a highly ordered structure of DNA and selected proteins capable to eliminate pathogenic microorganisms. Biochemical determinants of the non-randomly formed stable NETs have not been revealed so far. Studying the formation of human NETs we have observed that polyamines were incorporated into the NET. Inhibition of myeloperoxidase, which is essential for NET formation and can generate reactive chlorinated polyamines through hypochlorous acid, decreased polyamine incorporation. Addition of exogenous primary amines that similarly to polyamines inhibit reactions catalyzed by the protein cross-linker transglutaminases (TGases) has similar effect. Proteomic analysis of the highly reproducible pattern of NET components revealed cross-linking of NET proteins through chlorinated polyamines and epsilon(gamma-glutamyl) lysine as well as bis-gamma-glutamyl polyamine bonds catalyzed by the TGases detected in neutrophils. Competitive inhibition of protein cross-linking by monoamines disturbed the cross-linking pattern of NET proteins, which resulted in the loss of the ordered structure of the NET and significantly reduced capacity to trap bacteria. Our findings provide explanation of how NETs are formed in a reproducible and ordered manner to efficiently neutralize microorganisms at the first defense line of the innate immune system.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
NET
Megjelenés:Cell Death & Disease. - 7 : 8 (2016), p. e2332. -
További szerzők:Kristóf Endre (1987-) (általános orvos) Márkus Bernadett (1989-) (molekuláris biológus) Csomós István (1983-) (molekuláris biológus) Kovács György (1984-) (programtervező matematikus, fizikus) Rotem, Omri Hodrea Judit (1978-) (vegyész) Bagoly Zsuzsa (1978-) (orvos) Muszbek László (1942-) (haematológus, kutató orvos) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Csősz Éva (1977-) (biokémikus, molekuláris biológus) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0023
TÁMOP
TÁMOP-4.2.4.A/ 2-11/1-2012-0001
TÁMOP
OTKA NK 105046
OTKA
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM012860
Első szerző:Csomós Krisztián (molekuláris biológus)
Cím:Tissue transglutaminase contributes to the all-trans retinoic acid induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia / Csomós, K., Német, I., Fésüs, L., Balajthy, Z.
Dátum:2010
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Blood. - 116 : 19 (2010), p. 3933-3943. -
További szerzők:Német István (1982-) (Ph.D. hallgató, molekuláris biológus) Fésüs László (1947-) (orvos biokémikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
elektronikus változat
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5.

001-es BibID:BIBFORM049594
035-os BibID:PMID:23846866
Első szerző:Doan-Xuan, Quang-Minh (biofizikus)
Cím:High content analysis of differentiation and cell death in human adipocytes / Quang Minh Doan-Xuan, Anitta K. Sarvari, Pamela Fischer-Posovszky, Martin Wabitsch, Zoltan Balajthy, Laszlo Fesus, Zsolt Bacso
Dátum:2013
ISSN:1552-4922 1552-4930
Megjegyzések:Understanding adipocyte biology and its homeostasis is in the focus of current obesity research. We aimed to introduce a high-content analysis procedure for directly visualizing and quantifying adipogenesis and adipoapoptosis by laser scanning cytometry (LSC) in a large population of cell. Slide-based image cytometry and image processing algorithms were used and optimized for high-throughput analysis of differentiating cells and apoptotic processes in cell culture at high confluence. Both preadipocytes and adipocytes were simultaneously scrutinized for lipid accumulation, texture properties, nuclear condensation, and DNA fragmentation. Adipocyte commitment was found after incubation in adipogenic medium for 3 days identified by lipid droplet formation and increased light absorption, while terminal differentiation of adipocytes occurred throughout day 9-14 with characteristic nuclear shrinkage, eccentric nuclei localization, chromatin condensation, and massive lipid deposition. Preadipocytes were shown to be more prone to tumor necrosis factor alpha (TNFα)-induced apoptosis compared to mature adipocytes. Importantly, spontaneous DNA fragmentation was observed at early stage when adipocyte commitment occurs. This DNA damage was independent from either spontaneous or induced apoptosis and probably was part of the differentiation program.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
DNA damage
SGBS
adipocyte
differentiation
high content analysis
laser scanning cytometry
preadipocyte
Doktori iskola
Megjelenés:Cytometry Part A. - 83 : 10 (2013), p. 933-943. -
További szerzők:Sárvári Anitta Kinga (1984-) (biológus) Fischer-Posovszky Pamela Wabitsch, Martin Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Fésüs László (1947-) (orvos biokémikus) Bacsó Zsolt (1963-) (biofizikus)
Pályázati támogatás:NK 105046
OTKA
OMFB-01626/2006
OTKA
GVOP-3.2.1-2004-04-0351/3.0
GVOP
TECH09-A2-2009-0131
GVOP
TRANSCOM IAPP 251506
FP7
NKTH NTP Schizo08
Egyéb
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
Molekuláris Sejt- és Immunbiológiai Doktori Iskola
TÁMOP-4.2.2.A-11/1/KONV-2012-0023-"VÉD-ELEM"
TÁMOP
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM029009
Első szerző:Fésüs László (orvos biokémikus)
Cím:Transglutaminase induction by various cell death and apoptosis pathways / L. Fésüs, A. Mádi, Z. Balajthy, Z. Nemes, Zs. Szondy
Dátum:1996
Megjegyzések:Clarification of the molecular details of forms of natural cell death, including apoptosis, has become one of the most challenging issues of contemporary biomedical sciences. One of the effector elements of various cell death pathways is the covalent cross-linking of cellular proteins by transglutaminases. This review will discuss the accumulating data related to the induction and regulation of these enzymes, particularly of tissue type transglutaminase, in the molecular program of cell death. A wide range of signalling pathways can lead to the parallel induction of apoptosis and transglutaminase, providing a handle for better understanding the exact molecular interactions responsible for the mechanism of regulated cell death.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Experientia 52 : 10-11 (1996), p. 942-949. -
További szerzők:Mádi András (1967-) (biológus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Nemes Zoltán (1969-) (molekuláris biológus, pszichiáter) Szondy Zsuzsanna (1959-) (molekuláris sejtbiológus, biokémikus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM110245
035-os BibID:(cikkazonosító)217 (Scopus)85151110056 (WoS)000962544000005
Első szerző:Jambrovics Károly (biológus, gyógyszer-biotechnológus)
Cím:Transglutaminase 2 associated with PI3K and PTEN in a membrane-bound signalosome platform blunts cell death / Jambrovics Károly, Botó Pál, Pap Attila, Sarang Zsolt, Kolostyák Zsuzsanna, Czimmerer Zsolt, Szatmari Istvan, Fésüs László, Uray Iván P., Balajthy Zoltán
Dátum:2023
ISSN:2041-4889
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Cell Death & Disease. - 14 : 3 (2023), p. 1-10. -
További szerzők:Botó Pál (1986-) (molekuláris biológus) Pap Attila (1980-) (biológus) Sarang Zsolt (1976-) (mikrobiológus) Kolostyák Zsuzsanna Czimmerer Zsolt (1981-) (molekuláris biológus) Szatmári István (1971-) (biológus) Fésüs László (1947-) (orvos biokémikus) Uray Iván Péter (1970-) (kutatóorvos) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus)
Pályázati támogatás:K129139
OTKA
K129218
OTKA
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Intézményi repozitóriumban (DEA) tárolt változat
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8.

001-es BibID:BIBFORM084074
035-os BibID:(cikkazonosító)648 (WoS)000530232300124 (Scopus)85081217936
Első szerző:Jambrovics Károly (biológus, gyógyszer-biotechnológus)
Cím:Benefits of Combined All-Trans Retinoic Acid and Arsenic Trioxide Treatment of Acute Promyelocytic Leukemia Cells and Further Enhancement by Inhibition of Atypically Expressed Transglutaminase 2 / Jambrovics Károly, Uray Iván P., Keillor Jeffrey W., Fésüs László, Balajthy Zoltán
Dátum:2020
ISSN:2072-6694
Megjegyzések:Randomized trials in acute promyelocytic leukemia patients have shown that treatment with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) is superior in efficacy to monotherapy, with significantly decreased mortality. So far, there are little data available to explain the success of the ATRA and ATO combination treatment in molecular terms. We showed that ATRA- and ATO-treated cells had the same capacity for superoxide production, which was reduced by two-thirds in the combined treatment. Secreted inflammatory biomarkers (monocyte chemoattractant protein-1 [MCP-1], interleukin-1 beta [IL-1?] and tumor necrosis factor-? [TNF-?]) were significantly decreased and were further reduced in a transglutaminase 2 (TG2) expressiondependent manner. The amount of secreted TNF-? in the supernatant of NB4 TG2 knockout cells was close to 50 times lower than in ATRA-treated differentiated wild-type NB4 cells. The irreversible inhibitor of TG2 NC9 not only decreased reactive oxygen species production 28-fold, but decreased the concentration of MCP-1, IL-1? and TNF-? 8-, 15- and 61-fold, respectively in the combined ATRA + ATO-treated wild-type NB4 cell culture. We propose that atypical expression of TG2 leads to the generation of inflammation, which thereby serves as a potential target for the prevention of differentiation syndrome.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Cancers. - 12 : 3 (2020), p. 648-. -
További szerzők:Uray Iván Péter (1970-) (kutatóorvos) Keillor, Jeffrey W. Fésüs László (1947-) (orvos biokémikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00020
GINOP
K129218
OTKA
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Intézményi repozitóriumban (DEA) tárolt változat
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9.

001-es BibID:BIBFORM077169
035-os BibID:(WoS)000460110400026 (Scopus)85063936796
Első szerző:Jambrovics Károly (biológus, gyógyszer-biotechnológus)
Cím:Transglutaminase 2 programs differentiating acute promyelocytic leukemia cells in all-trans retinoic acid treatment to inflammatory stage through NF-kB activation / Jambrovics Károly, Uray Iván P., Keresztessy Zsolt, Keillor Jeffrey W., Fésüs László, Balajthy Zoltán
Dátum:2019
ISSN:0390-6078
Megjegyzések:Differentiation syndrome is a life-threatening complication arising during retinoid treatment of acute promyelocytic leukemia. Administration of all-trans retinoic acid leads to significant changes in gene expression, among the most induced of which is transglutaminase 2, which is not normally expressed in neutrophil granulocytes. To evaluate the pathophysiological function of transglutaminase 2 in the context of immunological function and disease outcomes, such as excessive superoxide anion, cytokine, and chemokine production in differentiated NB4 cells, we used an NB4 transglutaminase knock-out cell line and a transglutaminase inhibitor, NC9, which inhibits both transamidase- and guanosine triphosphate-binding activities, to clarify transglutaminase's contribution to the development of potentially lethal differentiation syndrome during all-trans retinoic acid treatment of acute promyelocytic leukemia. We found that such treatment not only enhanced cell-surface expression of CD11b and CD11c but also induced high-affinity states; atypical transglutaminase 2 expression in NB4 cells activated the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, driving pathogenic processes with an inflammatory cascade through the expression of numerous cytokines, including Tumor necrosis factor alpha, Interleukin 1 beta, and Monocyte chemoattractant protein 1. NC9 decreased the amount of transglutaminase 2, p65/RelA, and p50 in differentiated NB4 cells and their nuclei, leading to attenuated inflammatory cytokine synthesis. NC9 significantly inhibits transglutaminase 2 nuclear translocation but accelerates its proteasomal breakdown. This study demonstrates that transglutaminase 2 expression induced by all-trans retinoic acid treatment reprograms inflammatory signaling networks governed by nuclear factor kappa-light-chain-enhancer of activated B cells activation, resulting in over-expression of tumor necrosis factor alpha and Interleukin 1 beta in differentiating acute promyelocytic leukemia cells, suggesting that atypically expressed transglutaminase 2 is a promising target for leukemia treatment.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Haematologica-The Hematology Journal. - 104 : 3 (2019), p. 505-515. -
További szerzők:Uray Iván Péter (1970-) (kutatóorvos) Keresztessy Zsolt Keillor, Jeffrey W. Fésüs László (1947-) (orvos biokémikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00020
GINOP
TÁMOP-4.2.2.D-15/1/KONV-2015-0016
TÁMOP
EFOP-3.6.1-16-2016-00022
EFOP
GINOP-2.3.2-15-2016-00006
GINOP
NK105046
OTKA
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM040230
Első szerző:Keresztessy Zsolt
Cím:Phage display selection of efficient glutamine-donor substrate peptides for transglutaminase 2 / Keresztessy Z., Csosz E., Hársfalvi J., Csomós K., Gray J., Lightowlers R. N., Lakey J. H., Balajthy Z., Fésüs L.
Dátum:2006
ISSN:0961-8368
Megjegyzések:Understanding substrate specificity and identification of natural targets of transglutaminase 2 (TG2), the ubiquitous multifunctional cross-linking enzyme, which forms isopeptide bonds between protein-linked glutamine and lysine residues, is crucial in the elucidation of its physiological role. As a novel means of specificity analysis, we adapted the phage display technique to select glutamine-donor substrates from a random heptapeptide library via binding to recombinant TG2 and elution with a synthetic amine-donor substrate. Twenty-six Gln-containing sequences from the second and third biopanning rounds were susceptible for TG2-mediated incorporation of 5-(biotinamido)penthylamine, and the peptides GQQQTPY, GLQQASV, and WQTPMNS were modified most efficiently. A consensus around glutamines was established as pQX(P,T,S)l, which is consistent with identified substrates listed in the TRANSDAB database. Database searches showed that several proteins contain peptides similar to the phage-selected sequences, and the N-terminal glutamine-rich domain of SWI1/SNF1-related chromatin remodeling proteins was chosen for detailed analysis. MALDI/TOF and tandem mass spectrometry-based studies of a representative part of the domain, SGYGQQGQTPYYNQQSPHPQQQQPPYS (SnQ1), revealed that Q6, Q8, and Q22 are modified by TG2. Kinetic parameters of SnQ1 transamidation (KMapp = 250 mikroM, kcat = 18.3 sec-1, and kcat/KMapp = 73,200) classify it as an efficient TG2 substrate. Circular dichroism spectra indicated that SnQ1 has a random coil conformation, supporting its accessibility in the full-length parental protein. Added together, here we report a novel use of the phage display technology with great potential in transglutaminase research.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Protein Science. - 15 : 11 (2006), p. 2466-2480. -
További szerzők:Csősz Éva (1977-) (biokémikus, molekuláris biológus) Hársfalvi Jolán (1949-) (klinikai biokémikus) Csomós Krisztián (1981-) (molekuláris biológus) Gray, Joe Lightowlers, Robert N. Lakey, Jeremy H. Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Fésüs László (1947-) (orvos biokémikus)
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

001-es BibID:BIBFORM077512
Első szerző:Kristóf Endre (általános orvos)
Cím:Interleukin-6 released from differentiating human beige adipocytes improves browning / Endre Kristóf, Ágnes Klusóczki, Roland Veress, Abhirup Shaw, Zsolt Sándor Combi, Klára Varga, Ferenc Győry, Zoltán Balajthy, Péter Bai, Zsolt Bacso, László Fésüs
Dátum:2019
ISSN:0014-4827
Megjegyzések:Brown and beige adipocytes contribute significantly to the regulation of whole body energy expenditure and systemic metabolic homeostasis not exclusively by thermogenesis through mitochondrial uncoupling. Several studies have provided evidence in rodents that brown and beige adipocytes produce a set of adipokines ("batokines") which regulate local tissue homeostasis and have beneficial effects on physiological functions of the entire body. We observed elevated secretion of Interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1, but not tumor necrosis factor alpha (TNFα) or IL-1β pro-inflammatory cytokines, by ex vivo differentiating human beige adipocytes (induced by either PPARγ agonist or irisin) compared to white. Higher levels of IL-6, IL-8 and MCP-1 were released from human deep neck adipose tissue biopsies (enriched in browning cells) than from subcutaneous ones. IL-6 was produced in a sustained manner and mostly by the adipocytes and not by the undifferentiated progenitors. Continuous blocking of IL-6 receptor by specific antibody during beige differentiation resulted in downregulation of brown marker genes and increased morphological changes that are characteristic of white adipocytes. The data suggest that beige adipocytes adjust their production of IL-6 to reach an optimal level for differentiation in the medium enhancing browning in an autocrine manner.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Experimental Cell Research. - 377 : 1-2 (2019), p. 47-55. -
További szerzők:Klusóczki Ágnes (1991-) (biotechnológus) Veress Roland (1992-) (molekuláris biológus) Shaw, Abhirup (1992-) Combi Zsolt Varga Klára Győry Ferenc (1969-) (kardiológus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Bai Péter (1976-) (biokémikus) Bacsó Zsolt (1963-) (biofizikus) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
OTKA-NK105046
OTKA
OTKA-K123975
OTKA
ÚNKP-18-4
ÚNKP
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM065903
035-os BibID:(Scopus)85030708620 (WOS)000392133700005
Első szerző:Kristóf Endre (általános orvos)
Cím:Clozapine modifies the differentiation program of human adipocytes inducing browning / Endre Kristóf, Quang-Minh Doan-Xuan, Anitta Kinga Sárvári, Ágnes Klusóczki, Pamela Fischer-Posovszky, Martin Wabitsch, Zsolt Bacso, Péter Bai, Zoltán Balajthy, László Fésüs
Dátum:2016
Megjegyzések:Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not 6 other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser-scanning cytometry showed that up to 40% of the differentiating single primary and SGBS adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly up-regulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested if browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the up-regulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine induced beige cells displayed increased basal and oligomycin inhibited (proton leak) oxygen consumption but these cells showed a lower response to cAMP stimulus as compared to control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for treatment of SGA-induced weight gain.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adipocita
beige
clozapine
lézer-pásztázó citometria
elhízás
szerotonin
termogenezis
Megjelenés:Translational Psychiatry. - 6 : 11 (2016), p. 1-12. -
További szerzők:Doan-Xuan, Quang-Minh (1986-) (biofizikus) Sárvári Anitta Kinga (1984-) (biológus) Klusóczki Ágnes (1991-) (biotechnológus) Fischer-Posovszky Pamela Wabitsch, Martin Bacsó Zsolt (1963-) (biofizikus) Bai Péter (1976-) (biokémikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:TÁMOP-4.2.4.A/2-11/1-2012-0001
TÁMOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0023
TÁMOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0025
TÁMOP
TRANSCOM IAPP 251506
FP7
MTA-DE
MTA
Apoptózis és Genomika Kutatócsoport
K108308
OTKA
NK105046
OTKA
GINOP-2.3.2-15-2016-00006
GINOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:
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