@article{MTMT:33688209, title = {Organic anion transporting polypeptide 3A1 (OATP3A1)-gated bioorthogonal labeling of intracellular proteins}, url = {https://m2.mtmt.hu/api/publication/33688209}, author = {Németh, Krisztina and László, Zsófia and Biró, Adrienn and Szatmári, Ágnes and Cserép, Balázs Gergely and Várady, György and Bakos, Éva and Laczka, Csilla and Kele, Péter}, doi = {10.3390/molecules28062521}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {28}, unique-id = {33688209}, issn = {1420-3049}, abstract = {Organic anion transporting polypeptides (OATPs) were found to readily deliver membrane impermeable, tetrazine bearing fluorescent probes into cells. This feature was explored in OATP3A1 conditioned bio-orthogonal labeling schemes of various intracellular proteins in live cells. Confocal microscopy and super-resolution microscopy (STED) studies have shown that highly specific and efficient staining of the selected intracellular proteins can be achieved with the otherwise non-permeable probes when OATP3A1 is present in the cell membrane of cells. Such a transport protein linked bio-orthogonal labeling scheme is believed to be useful in OATP3A1 activity-controlled protein expression studies in the future. © 2023 by the authors.}, keywords = {PROTEINS; PROTEIN; Organic Anion Transporters; Flow Cytometry; Fluorescent Dyes; fluorescent dye; confocal microscopy; organic anion transporter; super-resolution microscopy; Cell permeability; Intracellular labeling; large Stokes shift fluorescent probes; live cell bio-orthogonal modification; organic anion transporter polypeptide 3A1; self-labeling enzyme tags}, year = {2023}, eissn = {1420-3049}, orcid-numbers = {Szatmári, Ágnes/0000-0001-8768-8212; Cserép, Balázs Gergely/0000-0002-0779-0338; Várady, György/0000-0003-2012-9680} } @article{MTMT:32172729, title = {A Genetically Encoded Isonitrile Lysine for Orthogonal Bioorthogonal Labeling Schemes}, url = {https://m2.mtmt.hu/api/publication/32172729}, author = {Szatmári, Ágnes and Cserép, Balázs Gergely and Molnár , Tibor Ákos and Söveges, Bianka and Biró, Adrienn and Várady, György and Szabó, Edit Zsuzsanna and Németh, Krisztina and Kele, Péter}, doi = {10.3390/molecules26164988}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {26}, unique-id = {32172729}, issn = {1420-3049}, year = {2021}, eissn = {1420-3049}, orcid-numbers = {Szatmári, Ágnes/0000-0001-8768-8212; Cserép, Balázs Gergely/0000-0002-0779-0338; Várady, György/0000-0003-2012-9680} } @article{MTMT:31861935, title = {Identification of Neuronal Pentraxins as Synaptic Binding Partners of C1q and the Involvement of NP1 in Synaptic Pruning in Adult Mice}, url = {https://m2.mtmt.hu/api/publication/31861935}, author = {Kovács, Réka and Vadászi, Henrietta and Bulyáki, Éva and Török, György and Tóth, Vilmos and Mátyás, Dominik and Kun, Judit and Hunyadi-Gulyás Éva, Csilla and Fedor, Flóra Zsófia and Csincsi, Ádám and Medzihradszky F., Katalin and Homolya, László and Juhász, Gábor Dénes and Kékesi, Adrienna Katalin and Józsi, Mihály and Györffy, Balázs A. and Kardos, József}, doi = {10.3389/fimmu.2020.599771}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {11}, unique-id = {31861935}, issn = {1664-3224}, year = {2021}, eissn = {1664-3224}, orcid-numbers = {Török, György/0000-0001-7616-5782; Fedor, Flóra Zsófia/0000-0003-4085-1419; Homolya, László/0000-0003-1639-8140; Juhász, Gábor Dénes/0000-0002-0849-6931; Kékesi, Adrienna Katalin/0000-0003-3042-4878; Józsi, Mihály/0000-0002-5520-5535; Kardos, József/0000-0002-2135-2932} } @article{MTMT:31523926, title = {Large Stokes-shift bioorthogonal probes for STED, 2P-STED and multi-color STED nanoscopy}, url = {https://m2.mtmt.hu/api/publication/31523926}, author = {Török, György and Cserép, Balázs Gergely and Telek, András and Arany, Dóra and Váradi, Melinda and Homolya, László and Kellermayer, Miklós and Kele, Péter and Németh, Krisztina}, doi = {10.1088/2050-6120/abb363}, journal-iso = {METHODS APPL FLUORESC}, journal = {METHODS AND APPLICATIONS IN FLUORESCENCE}, volume = {9}, unique-id = {31523926}, issn = {2050-6120}, year = {2021}, eissn = {2050-6120}, orcid-numbers = {Török, György/0000-0001-7616-5782; Cserép, Balázs Gergely/0000-0002-0779-0338; Telek, András/0000-0002-1909-8410; Váradi, Melinda/0000-0001-7733-0831; Homolya, László/0000-0003-1639-8140; Kellermayer, Miklós/0000-0002-5553-6553} } @article{MTMT:31678126, title = {Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell-based in vitro disease modeling: convergence of schizophrenia- and autism-related cellular phenotypes}, url = {https://m2.mtmt.hu/api/publication/31678126}, author = {Hathy, Edit Margit and Szabó, Eszter and Varga, Nóra and Erdei, Zsuzsa and Tordai, Csongor and Czehlár, Boróka and Baradits, Máté and Jezsó, Bálint and Koller, Júlia and Nagy, László and Molnár, Mária Judit and Homolya, László and Nemoda, Zsófia and Apáti, Ágota and Réthelyi, János}, doi = {10.1186/s13287-020-01980-5}, journal-iso = {STEM CELL RES THER}, journal = {STEM CELL RESEARCH & THERAPY}, volume = {11}, unique-id = {31678126}, issn = {1757-6512}, year = {2020}, eissn = {1757-6512}, orcid-numbers = {Hathy, Edit Margit/0000-0001-8977-5686; Tordai, Csongor/0000-0001-9770-997X; Baradits, Máté/0000-0003-1131-4550; Jezsó, Bálint/0000-0002-1306-4797; Koller, Júlia/0000-0003-3352-7450; Molnár, Mária Judit/0000-0001-9350-1864; Homolya, László/0000-0003-1639-8140; Nemoda, Zsófia/0000-0002-9550-7730; Réthelyi, János/0000-0002-3641-012X} } @article{MTMT:31177389, title = {Synaptic mitochondrial dysfunction and septin accumulation are linked to complement-mediated synapse loss in an Alzheimer’s disease animal model}, url = {https://m2.mtmt.hu/api/publication/31177389}, author = {Györffy, Balázs and Tóth, Vilmos and Török, György and Gulyássy, P. and Kovács, Réka and Vadászi, Henrietta and Micsonai, András and Tóth, Erzsébet Melinda and Sántha, Miklós and Homolya, László and Drahos, László and Juhász, Gábor Dénes and Kékesi, Adrienna Katalin and Kardos, József}, doi = {10.1007/s00018-020-03468-0}, journal-iso = {CELL MOL LIFE SCI}, journal = {CELLULAR AND MOLECULAR LIFE SCIENCES}, volume = {77}, unique-id = {31177389}, issn = {1420-682X}, abstract = {Synaptic functional disturbances with concomitant synapse loss represent central pathological hallmarks of Alzheimer’s disease. Excessive accumulation of cytotoxic amyloid oligomers is widely recognized as a key event that underlies neurodegeneration. Certain complement components are crucial instruments of widespread synapse loss because they can tag synapses with functional impairments leading to their engulfment by microglia. However, an exact understanding of the affected synaptic functions that predispose to complement-mediated synapse elimination is lacking. Therefore, we conducted systematic proteomic examinations on synaptosomes prepared from an amyloidogenic mouse model of Alzheimer’s disease (APP/PS1). Synaptic fractions were separated according to the presence of the C1q-tag using fluorescence-activated synaptosome sorting and subjected to proteomic comparisons. The results raised the decline of mitochondrial functions in the C1q-tagged synapses of APP/PS1 mice based on enrichment analyses, which was verified using flow cytometry. Additionally, proteomics results revealed extensive alterations in the level of septin protein family members, which are known to dynamically form highly organized pre- and postsynaptic supramolecular structures, thereby affecting synaptic transmission. High-resolution microscopy investigations demonstrated that synapses with considerable amounts of septin-3 and septin-5 show increased accumulation of C1q in APP/PS1 mice compared to the wild-type ones. Moreover, a strong positive correlation was apparent between synaptic septin-3 levels and C1q deposition as revealed via flow cytometry and confocal microscopy examinations. In sum, our results imply that deterioration of synaptic mitochondrial functions and alterations in the organization of synaptic septins are associated with complement-dependent synapse loss in Alzheimer’s disease. © 2020, The Author(s).}, keywords = {Complement C1q; Alzheimer's disease; mitochondrial dysfunction; Septins; synaptic pruning; Fluorescence-activated synaptosome sorting}, year = {2020}, eissn = {1420-9071}, pages = {5243-5258}, orcid-numbers = {Györffy, Balázs/0000-0003-0654-0641; Török, György/0000-0001-7616-5782; Micsonai, András/0000-0002-2539-4080; Homolya, László/0000-0003-1639-8140; Drahos, László/0000-0001-9589-6652; Juhász, Gábor Dénes/0000-0002-0849-6931; Kékesi, Adrienna Katalin/0000-0003-3042-4878; Kardos, József/0000-0002-2135-2932} } @article{MTMT:31139755, title = {The importance of transporters and cell polarization for the evaluation of human stem cell-derived hepatic cells}, url = {https://m2.mtmt.hu/api/publication/31139755}, author = {Török, György and Erdei, Zsuzsa and Lilienberg, Julianna and Apáti, Ágota and Homolya, László}, doi = {10.1371/journal.pone.0227751}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {15}, unique-id = {31139755}, issn = {1932-6203}, abstract = {One of the most promising applications of human pluripotent stem cells is their utilization for human-based pharmacological models. Despite the fact that membrane transporters expressed in the liver play pivotal role in various hepatic functions, thus far only little attention was devoted to the membrane transporter composition of the stem cell-derived liver models. In the present work, we have differentiated HUES9, a human embryonic stem cell line, toward the hepatic lineage, and monitored the expression levels of numerous differentiation marker and liver transporter genes with special focus on ABC transporters. In addition, the effect of bile acid treatment and polarizing culturing conditions on hepatic maturation has been assessed. We found that most transporter genes crucial for hepatic functions are markedly induced during hepatic differentiation; however, as regards the transporter composition the end-stage cells still exhibited dual, hepatocyte and cholangiocyte character. Although the bile acid treatment and sandwich culturing only slightly influenced the gene expressions, the stimulated cell polarization resulted in formation of bile canaliculi and proper localization of transporters. Our results point to the importance of membrane transporters in human stem cell-derived hepatic models and demonstrate the relevance of cell polarization in generation of applicable cellular models with correctly localized transporters. On the basis of our observations we suggest that conventional criteria for the evaluation of the quality of stem cell-derived hepatocyte-like cells ought to be augmented with additional elements, such as polarized and functional expression of hepatic transporters.}, year = {2020}, eissn = {1932-6203}, orcid-numbers = {Török, György/0000-0001-7616-5782; Homolya, László/0000-0003-1639-8140} } @article{MTMT:31069992, title = {A novel fluorescence-based functional assay for human OATP1A2 and OATP1C1 identifies interaction between third-generation P-gp inhibitors and OATP1A2}, url = {https://m2.mtmt.hu/api/publication/31069992}, author = {Bakos, Éva and Nemet, Orsolya and Patik, Izabel and Kucsma, Nóra and Várady, György and Szakács, Gergely and Laczka, Csilla}, doi = {10.1111/febs.15156}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, volume = {287}, unique-id = {31069992}, issn = {1742-464X}, abstract = {Organic anion-transporting polypeptide 1A2 (OATP1A2), expressed in the human blood-brain barrier, promotes drug uptake from the blood and hence can be exploited for central nervous system-targeted drug delivery. The thyroid transporter OATP1C1, expressed in the choroid plexus and in astrocytes, is also a potential pharmacological target. Based on their established pharmacological relevance, screening the drug interaction profile of OATP1A2 and OATP1C1 is highly desirable. However, drug interaction screens require suitable model systems and functional assays. In the current study, uptake of a set of cell-impermeable fluorescent dyes was screened in HEK-293 and A431 cell lines overexpressing OATP1A2 and OATP1C1. Based on the uptake of fluorescent dye substrates, a functional assay was developed, which was used to characterize OATP inhibitors/substrates. We identify Live/Dead Green (LDG), Live-or-Dye 488, and sulforhodamines 101, G, and B as novel fluorescent substrates of OATP1A2 and OATP1C1. We show that LDG uptake is proportional to OATP1A2/1C1 expression, allowing the isolation of cells expressing high transporter levels. Additionally, dye uptake can be used to characterize the drug interaction pattern of OATP1A2 and OATP1C1. We demonstrate that third-generation P-glycoprotein inhibitors elacridar, tariquidar, and zosuquidar inhibit OATP1A2 function. Increased toxicity of elacridar in OATP1A2-expressing cells suggests that OATP1A2 may modulate the distribution of this compound. The fluorescence-based assays developed in the current study are a good alternative of radioligand-based tests and pave the way toward high-throughput screens for OATP1A2/1C1 drug interaction studies.}, keywords = {Central Nervous System; fluorescent dye; OATP; P-gp inhibitor; drug interaction screen}, year = {2020}, eissn = {1742-4658}, pages = {2468-2485}, orcid-numbers = {Várady, György/0000-0003-2012-9680} } @article{MTMT:3387341, title = {Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning}, url = {https://m2.mtmt.hu/api/publication/3387341}, author = {Györffy, Balázs and Kun, Judit and Török, György and Bulyáki, Éva and Borhegyi, Zsolt and Gulyássy, Péter and Kis, Viktor and Szocsics, Péter and Micsonai, András and Matkó, János and Drahos, László and Juhász, Gábor Dénes and Kékesi, Adrienna Katalin and Kardos, József}, doi = {10.1073/pnas.1722613115}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {115}, unique-id = {3387341}, issn = {0027-8424}, abstract = {C1q, a member of the immune complement cascade, is implicated in the selective pruning of synapses by microglial phagocytosis. C1q-mediated synapse elimination has been shown to occur during brain development, while increased activation and complement-dependent synapse loss is observed in neurodegenerative diseases. However, the molecular mechanisms underlying C1q-controlled synaptic pruning are mostly unknown. This study addresses distortions in the synaptic proteome leading to C1q-tagged synapses. Our data demonstrated the preferential localization of C1q to the presynapse. Proteomic investigation and pathway analysis of C1q-tagged synaptosomes revealed the presence of apoptotic-like processes in C1q-tagged synapses, which was confirmed experimentally with apoptosis markers. Moreover, the induction of synaptic apoptotic-like mechanisms in a model of sensory deprivation-induced synaptic depression led to elevated C1q levels. Our results unveiled that C1q label-based synaptic pruning is triggered by and directly linked to apoptotic-like processes in the synaptic compartment.}, keywords = {Brain; SCHIZOPHRENIA; SYSTEM; ALZHEIMERS-DISEASE; PHOSPHATIDYLSERINE; ACTIVATION; CORTEX; C1q; Synaptosomes; VESICLE ENDOCYTOSIS}, year = {2018}, eissn = {1091-6490}, pages = {6303-6308}, orcid-numbers = {Györffy, Balázs/0000-0003-0654-0641; Török, György/0000-0001-7616-5782; Borhegyi, Zsolt/0000-0001-5556-8742; Micsonai, András/0000-0002-2539-4080; Drahos, László/0000-0001-9589-6652; Juhász, Gábor Dénes/0000-0002-0849-6931; Kékesi, Adrienna Katalin/0000-0003-3042-4878; Kardos, József/0000-0002-2135-2932} } @article{MTMT:2733708, title = {Efficient Generation of Human Embryonic Stem Cell-Derived Cardiac Progenitors Based on Tissue-Specific Enhanced Green Fluorescence Protein Expression}, url = {https://m2.mtmt.hu/api/publication/2733708}, author = {Szebényi, Kornélia and Péntek, Adrienn and Erdei, Zsuzsa and Várady, György and Orbán, Tamás I. and Sarkadi, Balázs and Apáti, Ágota}, doi = {10.1089/ten.TEC.2013.0646}, journal-iso = {TISSUE ENG PART C METHODS}, journal = {TISSUE ENGINEERING PART C METHODS}, volume = {21}, unique-id = {2733708}, issn = {1937-3384}, abstract = {Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven EGFP reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFPhigh rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFPhigh rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFPhigh rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications.}, year = {2015}, eissn = {1937-3392}, pages = {35-45}, orcid-numbers = {Szebényi, Kornélia/0000-0003-1558-8372; Várady, György/0000-0003-2012-9680; Orbán, Tamás I./0000-0002-3424-3428; Sarkadi, Balázs/0000-0003-0592-4539} }