TY - CONF AU - Igaz, Nóra AU - Szőke, Krisztina AU - Bocz, Csenge AU - Kovács, Dávid AU - Rónavári, Andrea AU - Szabó, Emilia Rita AU - Polanek, Róbert AU - Buhala, Andrea AU - Vizler, Csaba AU - Tiszlavicz, László AU - Rázga, Zsolt AU - Hideghéty, Katalin AU - Kónya, Zoltán AU - Csontné Kiricsi, Mónika TI - Radiosensitizing effect of metal nanoparticles in combination with histone deacetylase inhibitors T2 - FAMÉ 2023 PY - 2023 SP - 75 EP - 76 PG - 2 UR - https://m2.mtmt.hu/api/publication/34154565 ID - 34154565 LA - English DB - MTMT ER - TY - JOUR AU - Letoha, Annamária AU - Hudák, Anett AU - Bozsó, Zsolt AU - Vizler, Csaba AU - Veres, Gábor AU - Szilák, László AU - Letoha, Tamás TI - The Nuclear Localization Signal of NF-κB p50 Enters the Cells via Syndecan-Mediated Endocytosis and Inhibits NF-κB Activity JF - INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS J2 - INT J PEPT RES THER VL - 29 PY - 2023 IS - 5 PG - 16 SN - 1573-3149 DO - 10.1007/s10989-023-10548-9 UR - https://m2.mtmt.hu/api/publication/34050718 ID - 34050718 AB - It is well established that cationic peptides can enter cells following attachment to polyanionic membrane components. We report that the basic nuclear localization signal (NLS) of the NF-κB p50 subunit is internalized via lipid raft-dependent endocytosis mediated by heparan sulfate proteoglycans and exerts significant NF-κB inhibitory activities both in vitro and in vivo. In vitro uptake experiments revealed that the p50 NLS peptide (CYVQRKRQKLMP) enters the cytoplasm and accumulates in the nucleus at 37 °C. Depleting cellular ATP pools or decreasing temperature to 4 °C abolished peptide internalization, confirming the active, energy-dependent endocytic uptake. Co-incubation with heparan sulfate or replacing the peptide’s basic residues with glycines markedly reduced the intracellular entry of the p50 NLS, referring to the role of polyanionic cell-surface proteoglycans in internalization. Furthermore, treatment with methyl-β-cyclodextrin greatly inhibited the peptide’s membrane translocation. Overexpression of the isoforms of the syndecan family of transmembrane proteoglycans, especially syndecan-4, increased the cellular internalization of the NLS, suggesting syndecans’ involvement in the peptide’s cellular uptake. In vitro , p50 NLS reduced NF-κB activity in TNF-α-induced L929 fibroblasts and LPS-stimulated RAW 264.7 macrophages. TNF-α-induced ICAM-1 expression of HMEC-1 human endothelial cells could also be inhibited by the peptide. Fifteen minutes after its intraperitoneal injection, the peptide rapidly entered the cells of the pancreas, an organ with marked syndecan-4 expression. In an acute pancreatitis model, an inflammatory disorder triggered by the activation of stress-responsive transcription factors like NF-κB, administration of the p50 NLS peptide reduced the severity of pancreatic inflammation by blocking NF-κB transcription activity and ameliorating the examined laboratory and histological markers of pancreatitis. LA - English DB - MTMT ER - TY - JOUR AU - Varga-Zsíros, Vanda AU - Migh, Ede AU - Marton, Annamária AU - Kóta, Zoltán AU - Vizler, Csaba AU - Tiszlavicz, László AU - Horváth, Péter AU - Török, Zsolt AU - Vigh, László AU - Balogh, Gábor AU - Péter, Mária TI - Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 3 PG - 16 SN - 2073-4409 DO - 10.3390/cells12030428 UR - https://m2.mtmt.hu/api/publication/33607647 ID - 33607647 AB - Lipid metabolic disturbances are associated with several diseases, such as type 2 diabetes or malignancy. In the last two decades, high-performance mass spectrometry-based lipidomics has emerged as a valuable tool in various fields of biology. However, the evaluation of macroscopic tissue homogenates leaves often undiscovered the differences arising from micron-scale heterogeneity. Therefore, in this work, we developed a novel laser microdissection-coupled shotgun lipidomic platform, which combines quantitative and broad-range lipidome analysis with reasonable spatial resolution. The multistep approach involves the preparation of successive cryosections from tissue samples, cross-referencing of native and stained images, laser microdissection of regions of interest, in situ lipid extraction, and quantitative shotgun lipidomics. We used mouse liver and kidney as well as a 2D cell culture model to validate the novel workflow in terms of extraction efficiency, reproducibility, and linearity of quantification. We established that the limit of dissectible sample area corresponds to about ten cells while maintaining good lipidome coverage. We demonstrate the performance of the method in recognizing tissue heterogeneity on the example of a mouse hippocampus. By providing topological mapping of lipid metabolism, the novel platform might help to uncover region-specific lipidomic alterations in complex samples, including tumors. LA - English DB - MTMT ER - TY - JOUR AU - Gál, László AU - Bellák, Tamás AU - Marton, Annamária AU - Fekécs, Zoltán AU - Weissman, Drew AU - Török, Dénes AU - Biju, Rachana AU - Vizler, Csaba AU - Kristóf, Rebeka AU - Beattie, Mitchell B. AU - Lin, Paulo J.C. AU - Pardi, Norbert AU - Nógrádi, Antal AU - Pajer, Krisztián TI - Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA after Spinal Cord Injury JF - RESEARCH J2 - RESEARCH-CHINA VL - 6 PY - 2023 PG - 14 SN - 2096-5168 DO - 10.34133/research.0056 UR - https://m2.mtmt.hu/api/publication/33575768 ID - 33575768 N1 - Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary National Biotechnology Laboratory, Institute of Genetics, Biological Research Centre, Szeged, Hungary Institute of Biochemistry, Biological Research Centre, Szeged, Hungary Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada Export Date: 27 April 2023 Correspondence Address: Nógrádi, A.; Department of Anatomy, Hungary; email: nogradi.antal@med.u-szeged.hu Funding details: National Institutes of Health, NIH, 2020-1.1.6-JÖVŐ-2021-00012, 2022-2.1.1-NL-2022-00008, R01-AI153064 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, KLINO-117031 Funding text 1: We thank S. B. Sangeetham for the professional assistance (Department of Anatomy, Histology and Embryology, Szent-Györgyi Albert Medical School, University of Szeged). Funding: N.P. was supported by NIH R01-AI153064. C.V. and A.M. received generous support from the following grants: 2020-1.1.6-JÖVŐ-2021-00012 and 2022-2.1.1-NL-2022-00008 for the National Biotechnology Laboratory. A.N. was supported by the NKFIH KLINO-117031 grant. Author contributions: A.N., K.P., and L.G. designed the experiments. L.G., T.B., K.P., Z.F., and D.T. performed the surgical and gait analysis experiments. L.G. and R.B. collected the samples and managed all tissue processing, staining, and imaging. A.M. and C.V. performed and analyzed the proteome profiler and ELISA. M.B.B. and P.J.C.L. prepared the LNPs. R.K. performed the PCR experiments and data analysis. L.G., T.B., K.P., and Z.F. prepared the figures. A.N., K.P., and N.P. wrote the manuscript. N.P., D.W., M.B.B., P.J.C.L., and A.N. revised the manuscript. All authors discussed and helped prepare the manuscript. Competing interests: The authors declare that they have no competing interests. LA - English DB - MTMT ER - TY - JOUR AU - Hudak, Anett AU - Morgan, Gareth AU - Bacovsky, Jaromir AU - Patai, Roland AU - Polgár, Tamás Ferenc AU - Letoha, Annamaria AU - Pettkó-Szandtner, Aladár AU - Vizler, Csaba AU - Szilák, László AU - Letoha, Tamás TI - Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 14 PG - 17 SN - 1661-6596 DO - 10.3390/ijms23147609 UR - https://m2.mtmt.hu/api/publication/33050457 ID - 33050457 N1 - Funding Agency and Grant Number: Innovative Medicines Initiative 2 Joint Undertaking [807015]; European Union; EFPIA; European Union [863214]; National Research, Development, and Innovation Office, Hungary [2020-1.1.6-JOVO-2021-00012]; [2017-2.3.6-TET-CN-2018-00023] Funding text: A.H., L.S. and T.L. received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 807015. This joint undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. A.H., L.S. and T.L. also received funding from the European Union's Horizon 2020 research and innovation program under Future and Emerging Technologies grant agreement no. 863214. A.H., L.S. and T.L. were also supported by grant no. 2017-2.3.6-TET-CN-2018-00023. A.H., L.S., A.L., P.S.A., C.V. and T.L. were supported by grant no. 2020-1.1.6-JOVO-2021-00012 of the National Research, Development, and Innovation Office, Hungary. AB - Despite the growing list of identified SARS-CoV-2 receptors, the human angiotensin-converting enzyme 2 (ACE2) is still viewed as the main cell entry receptor mediating SARS-CoV-2 internalization. It has been reported that wild-type mice, like other rodent species of the Muridae family, cannot be infected with SARS-CoV-2 due to differences in their ACE2 receptors. On the other hand, the consensus heparin-binding motif of SARS-CoV-2's spike protein, PRRAR, enables the attachment to rodent heparan sulfate proteoglycans (HSPGs), including syndecans, a transmembrane HSPG family with a well-established role in clathrin- and caveolin-independent endocytosis. As mammalian syndecans possess a relatively conserved structure, we analyzed the cellular uptake of inactivated SARS-CoV-2 particles in in vitro and in vivo mice models. Cellular studies revealed efficient uptake into murine cell lines with established syndecan-4 expression. After intravenous administration, inactivated SARS-CoV-2 was taken up by several organs in vivo and could also be detected in the brain. Internalized by various tissues, inactivated SARS-CoV-2 raised tissue TNF-alpha levels, especially in the heart, reflecting the onset of inflammation. Our studies on in vitro and in vivo mice models thus shed light on unknown details of SARS-CoV-2 internalization and help broaden the understanding of the molecular interactions of SARS-CoV-2. LA - English DB - MTMT ER - TY - JOUR AU - Hudák, Anett AU - Letoha, Annamária AU - Vizler, Csaba AU - Letoha, Tamás TI - Syndecan-3 as a Novel Biomarker in Alzheimer's Disease. JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 6 SN - 1661-6596 DO - 10.3390/ijms23063407 UR - https://m2.mtmt.hu/api/publication/32758454 ID - 32758454 N1 - Cited By :2 Export Date: 26 April 2023 AB - Early diagnosis of Alzheimer's disease (AD) is of paramount importance in preserving the patient's mental and physical health in a fairly manageable condition for a longer period. Reliable AD detection requires novel biomarkers indicating central nervous system (CNS) degeneration in the periphery. Members of the syndecan family of transmembrane proteoglycans are emerging new targets in inflammatory and neurodegenerative disorders. Reviewing the growing scientific evidence on the involvement of syndecans in the pathomechanism of AD, we analyzed the expression of the neuronal syndecan, syndecan-3 (SDC3), in experimental models of neurodegeneration. Initial in vitro studies showed that prolonged treatment of tumor necrosis factor-alpha (TNF-α) increases SDC3 expression in model neuronal and brain microvascular endothelial cell lines. In vivo studies revealed elevated concentrations of TNF-α in the blood and brain of APPSWE-Tau transgenic mice, along with increased SDC3 concentration in the brain and the liver. Primary brain endothelial cells and peripheral blood monocytes isolated from APPSWE-Tau mice exhibited increased SDC3 expression than wild-type controls. SDC3 expression of blood-derived monocytes showed a positive correlation with amyloid plaque load in the brain, demonstrating that SDC3 on monocytes is a good indicator of amyloid pathology in the brain. Given the well-established role of blood tests, the SDC3 expression of monocytes could serve as a novel biomarker for early AD detection. LA - English DB - MTMT ER - TY - CONF AU - Bellák, Tamás AU - Pajer, Krisztián AU - Gál, László AU - Marton, Annamária AU - Vizler, Csaba AU - Fekécs, Zoltán AU - Nógrádi, Antal TI - Modulatory effects of grafted neuroectodermal stem cells after chronic spinal cord contusion injury T2 - Virtual FENS Regional Meeting 2021 PY - 2021 SP - 78 EP - 78 PG - 1 UR - https://m2.mtmt.hu/api/publication/32290397 ID - 32290397 LA - English DB - MTMT ER - TY - JOUR AU - Bajusz, Csaba AU - Kristó, Ildikó AU - Abonyi, Csilla AU - Venit, Tomáš AU - Vedelek, Viktor AU - Lukácsovich, Tamás AU - Farkas, Attila AU - Borkúti, Péter AU - Kovács, Zoltán AU - Bajusz, Izabella AU - Marton, Annamária AU - Vizler, Csaba AU - Lipinszki, Zoltán AU - Sinka, Rita AU - Percipalle, Piergiorgio AU - Vilmos, Péter TI - The nuclear activity of the actin‐binding Moesin protein is necessary for gene expression in Drosophila JF - FEBS JOURNAL J2 - FEBS J VL - 288 PY - 2021 IS - 16 SP - 4812 EP - 4832 PG - 21 SN - 1742-464X DO - 10.1111/febs.15779 UR - https://m2.mtmt.hu/api/publication/31909117 ID - 31909117 N1 - Eötvös Loránd Research Network (ELKH), Biological Research Centre, Szeged, Hungary Doctoral School of Biology, University of Szeged, Hungary Department of Genetics, University of Szeged, Hungary Doctoral School of Multidisciplinary Medical Science, University of Szeged, Hungary Lendület Laboratory of Cell Cycle Regulation, ELKH, Biological Research Centre, Szeged, Hungary LA - English DB - MTMT ER - TY - JOUR AU - Asperger, Hannah AU - Stamm, Nadia AU - Gierke, Berthold AU - Pawlak, Michael AU - Hofmann, Ute AU - Zanger, Ulrich M. AU - Marton, Annamária AU - Katona, Róbert László AU - Buhala, Andrea AU - Vizler, Csaba AU - Cieslik, Jan-Philipp AU - Kovacevic, Zaklina AU - Richardson, Des R. AU - Ruckhaeberle, Eugen AU - Niederacher, Dieter AU - Fehm, Tanja AU - Neubauer, Hans AU - Ludescher, Marina TI - Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression (vol 22, 75, 2020) JF - BREAST CANCER RESEARCH J2 - BREAST CANCER RES VL - 23 PY - 2021 IS - 1 SN - 1465-5411 DO - 10.1186/s13058-020-01383-7 UR - https://m2.mtmt.hu/api/publication/31873459 ID - 31873459 AB - An amendment to this paper has been published and can be accessed via the original article. LA - English DB - MTMT ER - TY - JOUR AU - Asperger, Hannah AU - Stamm, Nadia AU - Gierke, Berthold AU - Pawlak, Michael AU - Hofmann, Ute AU - Zanger, Ulrich M. AU - Marton, Annamária AU - Katona, Róbert László AU - Buhala, Andrea AU - Vizler, Csaba AU - Cieslik, Jan-Philipp AU - Ruckhaeberle, Eugen AU - Niederacher, Dieter AU - Fehm, Tanja AU - Neubauer, Hans AU - Ludescher, Marina TI - Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression JF - BREAST CANCER RESEARCH J2 - BREAST CANCER RES VL - 22 PY - 2020 IS - 1 SN - 1465-5411 DO - 10.1186/s13058-020-01312-8 UR - https://m2.mtmt.hu/api/publication/31397452 ID - 31397452 AB - Background: PGRMC1 (progesterone receptor membrane component 1) is a highly conserved heme binding protein, which is overexpressed especially in hormone receptor-positive breast cancer and plays an important role in breast carcinogenesis. Nevertheless, little is known about the mechanisms by which PGRMC1 drives tumor progression. The aim of our study was to investigate the involvement of PGRMC1 in cholesterol metabolism to detect new mechanisms by which PGRMC1 can increase lipid metabolism and alter cancer-related signaling pathways leading to breast cancer progression. Methods: The effect of PGRMC1 overexpression and silencing on cellular proliferation was examined in vitro and in a xenograft mouse model. Next, we investigated the interaction of PGRMC1 with enzymes involved in the cholesterol synthesis pathway such as CYP51, FDFT1, and SCD1. Further, the impact of PGRMC1 expression on lipid levels and expression of enzymes involved in lipid homeostasis was examined. Additionally, we assessed the role of PGRMC1 in key cancer-related signaling pathways including EGFR/HER2 and ER alpha signaling. Results: Overexpression of PGRMC1 resulted in significantly enhanced proliferation. PGRMC1 interacted with key enzymes of the cholesterol synthesis pathway, alters the expression of proteins, and results in increased lipid levels. PGRMC1 also influenced lipid raft formation leading to altered expression of growth receptors in membranes of breast cancer cells. Analysis of activation of proteins revealed facilitated ER alpha and EGFR activation and downstream signaling dependent on PGRMC1 overexpression in hormone receptor-positive breast cancer cells. Depletion of cholesterol and fatty acids induced by statins reversed this growth benefit. Conclusion: PGRMC1 may mediate proliferation and progression of breast cancer cells potentially by altering lipid metabolism and by activating key oncogenic signaling pathways, such as ER alpha expression and activation, as well as EGFR signaling. Our present study underlines the potential of PGRMC1 as a target for anti-cancer therapy. LA - English DB - MTMT ER -