@CONFERENCE{MTMT:34154565, title = {Radiosensitizing effect of metal nanoparticles in combination with histone deacetylase inhibitors}, url = {https://m2.mtmt.hu/api/publication/34154565}, author = {Igaz, Nóra and Szőke, Krisztina and Bocz, Csenge and Kovács, Dávid and Rónavári, Andrea and Szabó, Emilia Rita and Polanek, Róbert and Buhala, Andrea and Vizler, Csaba and Tiszlavicz, László and Rázga, Zsolt and Hideghéty, Katalin and Kónya, Zoltán and Csontné Kiricsi, Mónika}, booktitle = {FAMÉ 2023}, unique-id = {34154565}, year = {2023}, pages = {75-76}, orcid-numbers = {Igaz, Nóra/0000-0003-1580-4397; Rónavári, Andrea/0000-0001-7054-0975; Szabó, Emilia Rita/0000-0003-3611-2066; Polanek, Róbert/0000-0003-3645-8331; Tiszlavicz, László/0000-0003-1134-6587; Rázga, Zsolt/0000-0003-4717-8482; Hideghéty, Katalin/0000-0001-7080-2365; Kónya, Zoltán/0000-0002-9406-8596; Csontné Kiricsi, Mónika/0000-0002-8416-2052} } @article{MTMT:34050718, title = {The Nuclear Localization Signal of NF-κB p50 Enters the Cells via Syndecan-Mediated Endocytosis and Inhibits NF-κB Activity}, url = {https://m2.mtmt.hu/api/publication/34050718}, author = {Letoha, Annamária and Hudák, Anett and Bozsó, Zsolt and Vizler, Csaba and Veres, Gábor and Szilák, László and Letoha, Tamás}, doi = {10.1007/s10989-023-10548-9}, journal-iso = {INT J PEPT RES THER}, journal = {INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS}, volume = {29}, unique-id = {34050718}, issn = {1573-3149}, abstract = {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.}, year = {2023}, eissn = {1573-3904}, orcid-numbers = {Bozsó, Zsolt/0000-0002-5713-3096} } @article{MTMT:33607647, title = {Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity}, url = {https://m2.mtmt.hu/api/publication/33607647}, author = {Varga-Zsíros, Vanda and Migh, Ede and Marton, Annamária and Kóta, Zoltán and Vizler, Csaba and Tiszlavicz, László and Horváth, Péter and Török, Zsolt and Vigh, László and Balogh, Gábor and Péter, Mária}, doi = {10.3390/cells12030428}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {33607647}, abstract = {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.}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773; Tiszlavicz, László/0000-0003-1134-6587} } @article{MTMT:33575768, title = {Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA after Spinal Cord Injury}, url = {https://m2.mtmt.hu/api/publication/33575768}, author = {Gál, László and Bellák, Tamás and Marton, Annamária and Fekécs, Zoltán and Weissman, Drew and Török, Dénes and Biju, Rachana and Vizler, Csaba and Kristóf, Rebeka and Beattie, Mitchell B. and Lin, Paulo J.C. and Pardi, Norbert and Nógrádi, Antal and Pajer, Krisztián}, doi = {10.34133/research.0056}, journal-iso = {RESEARCH-CHINA}, journal = {RESEARCH}, volume = {6}, unique-id = {33575768}, issn = {2096-5168}, year = {2023}, eissn = {2639-5274} } @article{MTMT:33050457, title = {Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice}, url = {https://m2.mtmt.hu/api/publication/33050457}, author = {Hudak, Anett and Morgan, Gareth and Bacovsky, Jaromir and Patai, Roland and Polgár, Tamás Ferenc and Letoha, Annamaria and Pettkó-Szandtner, Aladár and Vizler, Csaba and Szilák, László and Letoha, Tamás}, doi = {10.3390/ijms23147609}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33050457}, issn = {1661-6596}, abstract = {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.}, keywords = {MECHANISMS; PROTEIN; MEMBRANE; IMMUNODEFICIENCY-VIRUS TYPE-1; ENDOCYTOSIS; Proteoglycans; Heparan Sulfate Proteoglycans; CELLULAR UPTAKE; Syndecans; Syndecans; Biochemistry & Molecular Biology; COVID-19; SARS-CoV-2; ARGININE-RICH PEPTIDES}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Letoha, Tamás/0000-0002-6035-4009} } @article{MTMT:32758454, title = {Syndecan-3 as a Novel Biomarker in Alzheimer's Disease.}, url = {https://m2.mtmt.hu/api/publication/32758454}, author = {Hudák, Anett and Letoha, Annamária and Vizler, Csaba and Letoha, Tamás}, doi = {10.3390/ijms23063407}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {32758454}, issn = {1661-6596}, abstract = {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.}, keywords = {Brain; MONOCYTES; BLOOD; Biomarkers; Blood-Brain Barrier; Alzheimer's disease; syndecan-3}, year = {2022}, eissn = {1422-0067} } @CONFERENCE{MTMT:32290397, title = {Modulatory effects of grafted neuroectodermal stem cells after chronic spinal cord contusion injury}, url = {https://m2.mtmt.hu/api/publication/32290397}, author = {Bellák, Tamás and Pajer, Krisztián and Gál, László and Marton, Annamária and Vizler, Csaba and Fekécs, Zoltán and Nógrádi, Antal}, booktitle = {Virtual FENS Regional Meeting 2021}, unique-id = {32290397}, year = {2021}, pages = {78-78} } @article{MTMT:31909117, title = {The nuclear activity of the actin‐binding Moesin protein is necessary for gene expression in Drosophila}, url = {https://m2.mtmt.hu/api/publication/31909117}, author = {Bajusz, Csaba and Kristó, Ildikó and Abonyi, Csilla and Venit, Tomáš and Vedelek, Viktor and Lukácsovich, Tamás and Farkas, Attila and Borkúti, Péter and Kovács, Zoltán and Bajusz, Izabella and Marton, Annamária and Vizler, Csaba and Lipinszki, Zoltán and Sinka, Rita and Percipalle, Piergiorgio and Vilmos, Péter}, doi = {10.1111/febs.15779}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, volume = {288}, unique-id = {31909117}, issn = {1742-464X}, year = {2021}, eissn = {1742-4658}, pages = {4812-4832}, orcid-numbers = {Lipinszki, Zoltán/0000-0002-2067-0832; Sinka, Rita/0000-0003-4040-4184; Vilmos, Péter/0000-0001-5692-8818} } @article{MTMT:31873459, title = {Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression (vol 22, 75, 2020)}, url = {https://m2.mtmt.hu/api/publication/31873459}, author = {Asperger, Hannah and Stamm, Nadia and Gierke, Berthold and Pawlak, Michael and Hofmann, Ute and Zanger, Ulrich M. and Marton, Annamária and Katona, Róbert László and Buhala, Andrea and Vizler, Csaba and Cieslik, Jan-Philipp and Kovacevic, Zaklina and Richardson, Des R. and Ruckhaeberle, Eugen and Niederacher, Dieter and Fehm, Tanja and Neubauer, Hans and Ludescher, Marina}, doi = {10.1186/s13058-020-01383-7}, journal-iso = {BREAST CANCER RES}, journal = {BREAST CANCER RESEARCH}, volume = {23}, unique-id = {31873459}, issn = {1465-5411}, abstract = {An amendment to this paper has been published and can be accessed via the original article.}, year = {2021}, eissn = {1465-542X} } @article{MTMT:31397452, title = {Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression}, url = {https://m2.mtmt.hu/api/publication/31397452}, author = {Asperger, Hannah and Stamm, Nadia and Gierke, Berthold and Pawlak, Michael and Hofmann, Ute and Zanger, Ulrich M. and Marton, Annamária and Katona, Róbert László and Buhala, Andrea and Vizler, Csaba and Cieslik, Jan-Philipp and Ruckhaeberle, Eugen and Niederacher, Dieter and Fehm, Tanja and Neubauer, Hans and Ludescher, Marina}, doi = {10.1186/s13058-020-01312-8}, journal-iso = {BREAST CANCER RES}, journal = {BREAST CANCER RESEARCH}, volume = {22}, unique-id = {31397452}, issn = {1465-5411}, abstract = {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.}, year = {2020}, eissn = {1465-542X} }