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001-es BibID:	BIBFORM066424
Első szerző:	Kristóf Endre (általános orvos)
Cím:	Role of ICAM3 in the interaction between human macrophages and apoptotic neutrophil granulocytes / E. K. Kristóf, G. Zahuczky, L. Fésüs
Dátum:	2011
ISSN:	1742-464X
Megjegyzések:	The daily clearance of billions of physiologically dying cells in the human body is performed safely mainly by the mononuclear phagocyte system Bridging molecules and receptors ? which recognize the dying cells ? show high redundancy and are linked to several intracellular signaling pathways. Our previous ♭Taq-Man Low Density Array' measurements predicted important role of many genes in phagocytosis, because their expression level heavily elevated during the early stage of the phagocytosis process. The four genes (ADORA2A, FPRL1, ICAM3, THBS1)with the most enhanced expression in human macrophages wereknocked-down by RNA interference which was controlled byWestern-blot and surface immunostaining at translational level. Significant decrease in phagocytic capacity was observed only after silencing ICAM3. Our goal was to investigate the role and interacting partners of ICAM3 transmembrane protein from both sides. Human monocytes were isolated from ♭buffy coats' of healthy blood by magnetic separation using CD14 human microbeads. To examine the phagocytic capacity of 5 day differentiated macrophages, apoptotic neutrophil granulocytes were isolated from human blood by Histopaque density-gradient centrifugation. The phagocytosis assay was performed using fluorescent labeled cells and the incorporated cell-rate was measured by flow cytometry, immediately after pre-incubation of macrophages or apoptotic cells with blocking antibodies. Significant reduction of phagocytosis was noticed after blocking ICAM3 from both sides while that of DC-SIGN, which is a cited receptor for ICAM3, did not influence the engulfment of apoptotic cells. ICAM-3 participates in the recognition of apoptotic neutrophils by macrophages from both sides not only as an adhesion molecule but also as an initiator of signaling pathways mediated by intracellular thyrosin kinases. To examine its interacting partners in this process further investigations have to be performed in the future.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt Molekuláris Medicina
Megjelenés:	FEBS Journal 278 : Suppl. 1 (2011), p. 138. -
További szerzők:	Zahuczky Gábor (1975-) (molekuláris biológus, biokémikus, vegyész) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Az apoptózis molekuláris mechanizmusa NI 67877 OTKA
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001-es BibID:	BIBFORM066410
Első szerző:	Kristóf Endre (általános orvos)
Cím:	Role of ICAM3 and its interacting partners in the phagocytosis of apoptotic neutrophils by macrophages / E. K. Kristóf, G. Zahuczky, L. Fésüs
Dátum:	2012
ISSN:	1742-464X
Megjegyzések:	Apoptotic cells express eat-me signals which are recognized by several receptors mainly on professional phagocytes that can define their safe and effective clearance in order to maintain tissue homeostasis in the entire body. TLDA measurements predicted important role of some apopto-phagocytic genes in phagocytosis of apoptotic neutrophils by macrophages, because their expression level heavily elevated during the early stage of phagocytosis. After they were silenced by RNA interference, significant decrease in phagocytosis was observed only after silencing ICAM3. Our goal was to investigate the role and interacting partners of ICAM3 from both sides. Monocytes were isolated from buffy coats of healthy blood by CD14 specific magnetic separation. To examine phagocytic capacity of differentiated macrophages, apoptotic neutrophils were isolated from human blood by density-gradient centrifugation. Phagocytosis assay was performed using fluorescent labeled cells and the incorporated cell-rate was measured by flow cytometry, immediately after preincubation of macrophages or apoptotic cells with blocking antibodies. Localization of the investigated receptors was visualized by indirect immunostaining. Significant reduction of phagocytosis was noticed after blocking of ICAM3 from both sides. In macrophages but not in neutrophils silencing and blocking components of LFA-1, which can strongly bind ICAM3, resulted in a decreased phagocytosis of apoptotic cells. Engulfing caps formed in macrophages during phagocytosis are characterized by accumulation of ICAM3 and the subunits of LFA-1 which show colocalization on the surface of phagocytes showing that ICAM3 and LFA-1 act as recognition receptors in the phagocytosis portals of macrophages for engulfment of apoptotic neutrophils.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok poszter Molekuláris Medicina Doktori iskola
Megjelenés:	FEBS Journal 279 : Suppl. 1 (2012), p. 52. -
További szerzők:	Zahuczky Gábor (1975-) (molekuláris biológus, biokémikus, vegyész) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:	NK 105046 OTKA K 61868 OTKA TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Az apoptózis molekuláris mechanizmusa TÁMOP-4.2.2/B-10/1-2010-0024 TÁMOP Molekuláris Sejt- és Immunbiológia Doktori Iskola TRANSCOM IAPP251506 FP7 TRANSPATH ITN 289964 FP7
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM066382
Első szerző:	Kristóf Endre (általános orvos)
Cím:	Irisin modifies the differentiation program of subcutaneous human adipocytes and induces "browning" / E. K. Kristof, Q. M. Doan-Xuan, P. Bai, Z. Bacsó, L. Fésüs
Dátum:	2014
ISSN:	1742-464X
Megjegyzések:	Although brown adipose tissue (BAT) can be found only in small amounts in the human body after infancy, recent studies revealed that it has a major importance in regulating the energy balance of the entire body. Its oxidative metabolism contributes to energy expenditure during cold exposure and diet or physical exercise induced thermogenesis by triggering the differentiation of"brown adipocyte-like" or "beige" cells interspersed in subcutaneous white adipose tissue depots in a process called "browning". A very strong negative correlation has been found between obesity and BAT amount in humans. Targeting the currently known and unknown regulatory systems of "browning" might open up better strategies to specifically stimulate BAT in obese individuals to aidweight reduction.Irisin is a recently identified peptide hormone which is cleaved from the Fndc5 transmembrane protein and induces a "browning" program in subcutaneous white adipose tissue in mouse models. In humans, however, an escalating debate revolves around the secretion and metabolic effects of irisin. Our aim was to clarify whether human recombinant irsin was able to induce a browning program on differentiating human adipocytes.Human primary preadipocytes obtained from herniotomy were differentiated into white or brown adipocytes with or without long or short-term irisin treatment. Expression of white, brown and general adipocyte markers were determined by RT Q-PCR,immunoblotting or immunocytochemistry and changes in morphology (size and number of lipid droplets, expression of Ucp1 and Cidea in situ) were visualized and quantified by Laser Scanning Cytometry. Functional analysis was carried out using a Seahorse Bioscience XF-96 Analyzer.Irisin administration during white adipogenic differentiation resulted in a significant overexpression of several brown adipocyte marker genes (UCP1, ELOVL3, CIDEA, CYC1, PGC1A). Irisin treated cells had more and smaller lipid droplets, more mitochondrial DNA, higher functional mitochondrial respiration and expressed more Ucp1 and Cidea in situ than the in vitro differentiated white adipocytes. We conclude that irisin treatment is able to induce a browning program in differentiating human subcutaneous white adipocytes in culture conditions.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt Browning Irisin Laser Scanning Cytometry
Megjelenés:	Febs Journal 281 : Suppl. 1 (2014), p. 230. -
További szerzők:	Doan-Xuan, Quang-Minh (1986-) (biofizikus) Bai Péter (1976-) (biokémikus) Bacsó Zsolt (1963-) (biofizikus) 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 MTA-DE MTA Apoptózis és Genomika Kutatócsoport
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM060597
Első szerző:	Kristóf Endre (általános orvos)
Cím:	Second generation antipsychotic (SGA) drugs modify the differentiation program of human adipocytes inducing 'browning' markers / E. Kristof, D. Minh, A. Sarvari, Z. Balajthy, Z. Bacso, L. Fesus
Dátum:	2013
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:	FEBS journal 280 : 1 (2013), p. 289. -
További szerzők:	Doan-Xuan, Quang-Minh (1986-) (biofizikus) Sárvári Anitta Kinga (1984-) (biológus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Bacsó Zsolt (1963-) (biofizikus) Fésüs László (1947-) (orvos biokémikus)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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