@article{MTMT:32930192, title = {The Small Heat Shock Protein, HSPB1, Interacts with and Modulates the Physical Structure of Membranes}, url = {https://m2.mtmt.hu/api/publication/32930192}, author = {Csoboz, Bálint and Gombos, Imre and Kóta, Zoltán and Dukic, Barbara and Klement, Éva and Varga-Zsíros, Vanda and Lipinszki, Zoltán and Páli, Tibor and Vigh, László and Török, Zsolt}, doi = {10.3390/ijms23137317}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {32930192}, issn = {1661-6596}, abstract = {Small heat shock proteins (sHSPs) have been demonstrated to interact with lipids and modulate the physical state of membranes across species. Through these interactions, sHSPs contribute to the maintenance of membrane integrity. HSPB1 is a major sHSP in mammals, but its lipid interaction profile has so far been unexplored. In this study, we characterized the interaction between HSPB1 and phospholipids. HSPB1 not only associated with membranes via membrane-form-ing lipids, but also showed a strong affinity towards highly fluid membranes. It participated in the modulation of the physical properties of the interacting membranes by altering rotational and lat-eral lipid mobility. In addition, the in vivo expression of HSPB1 greatly affected the phase behavior of the plasma membrane under membrane fluidizing stress conditions. In light of our current find-ings, we propose a new function for HSPB1 as a membrane chaperone. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {membrane fluidity; stress response; lipid-protein interaction; Membrane chaperone; small HSP}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773; Lipinszki, Zoltán/0000-0002-2067-0832; Páli, Tibor/0000-0003-1649-1097} } @article{MTMT:32849807, title = {Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells.}, url = {https://m2.mtmt.hu/api/publication/32849807}, author = {Tiszlavicz, Ádám and Gombos, Imre and Péter, Mária and Hegedűs, Zoltán and Hunya, Ákos and Dukic, Barbara and Nagy, István and Peksel, Begüm and Balogh, Gábor and Horváth, Ibolya and Vigh, László and Török, Zsolt}, doi = {10.3390/biomedicines10051172}, journal-iso = {BIOMEDICINES}, journal = {BIOMEDICINES}, volume = {10}, unique-id = {32849807}, abstract = {Mild stress could help cells to survive more severe environmental or pathophysiological conditions. In the current study, we investigated the cellular mechanisms which contribute to the development of stress tolerance upon a prolonged (0-12 h) fever-like (40 °C) or a moderate (42.5 °C) hyperthermia in mammalian Chinese Hamster Ovary (CHO) cells. Our results indicate that mild heat triggers a distinct, dose-dependent remodeling of the cellular lipidome followed by the expression of heat shock proteins only at higher heat dosages. A significant elevation in the relative concentration of saturated membrane lipid species and specific lysophosphatidylinositol and sphingolipid species suggests prompt membrane microdomain reorganization and an overall membrane rigidification in response to the fluidizing heat in a time-dependent manner. RNAseq experiments reveal that mild heat initiates endoplasmic reticulum stress-related signaling cascades resulting in lipid rearrangement and ultimately in an elevated resistance against membrane fluidization by benzyl alcohol. To protect cells against lethal, protein-denaturing high temperatures, the classical heat shock protein response was required. The different layers of stress response elicited by different heat dosages highlight the capability of cells to utilize multiple tools to gain resistance against or to survive lethal stress conditions.}, keywords = {MEMBRANE; STRESS; heat shock response; transcriptomics; LIPIDOMICS; Unfolded protein response; Chinese hamster ovary cells; acquired stress tolerance; membrane lipid metabolism}, year = {2022}, eissn = {2227-9059}, orcid-numbers = {Hunya, Ákos/0000-0002-4547-9284} } @article{MTMT:32515212, title = {Nicotinic Amidoxime Derivate BGP-15, Topical Dosage Formulation and Anti-Inflammatory Effect}, url = {https://m2.mtmt.hu/api/publication/32515212}, author = {Pető, Ágota and Kósa, Dóra and Haimhoffer, Ádám and Siposné Fehér, Pálma and Ujhelyi, Zoltán and Sinka, Dávid and Fenyvesi, Ferenc and Váradi, Judit and Vecsernyés, Miklós and Gyöngyösi, Alexandra and Lekli, István and Szentesi, Péter and Marton, Annamária and Gombos, Imre and Dukic, Barbara and Vigh, László and Bácskay, Ildikó}, doi = {10.3390/pharmaceutics13122037}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {13}, unique-id = {32515212}, issn = {1999-4923}, abstract = {BGP-15 is a Hungarian-developed drug candidate with numerous beneficial effects. Its potential anti-inflammatory effect is a common assumption, but it has not been investigated in topical formulations yet. The aim of our study was to formulate 10% BGP-15 creams with different penetration enhancers to ensure good drug delivery, improve bioavailability of the drug and investigate the potential anti-inflammatory effect of BGP-15 creams in vivo. Since the exact mechanism of the effect is still unknown, the antioxidant effect (tested with UVB radiation) and the ability of BGP-15 to decrease macrophage activation were evaluated. Biocompatibility investigations were carried out on HaCaT cells to make sure that the formulations and the selected excipients can be safely used. Dosage form studies were also completed with texture analysis and in vitro release with Franz diffusion chamber apparatus. Our results show that the ointments were able to reduce the extent of local inflammation in mice, but the exact mechanism of the effect remains unknown since BGP-15 did not show any antioxidant effect, nor was it able to decrease LPS-induced macrophage activation. Our results support the hypothesis that BGP-15 has a potential anti-inflammatory effect, even if it is topically applied, but the mechanism of the effect remains unclear and requires further pharmacological studies.}, keywords = {ANTIOXIDANT; Drug delivery; Ointments; SURFACTANTS; BGP-15; PARP inhibitor; Anti-inflammatory drug; Dosage formulation; Dosage formulation; Nicotinic amidoxime derivate; Nicotinic amidoxime derivate}, year = {2021}, eissn = {1999-4923}, orcid-numbers = {Szentesi, Péter/0000-0003-2621-2282} } @article{MTMT:31319639, title = {Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells}, url = {https://m2.mtmt.hu/api/publication/31319639}, author = {Crul, Tim and Csoboz, Bálint and Gombos, Imre and Marton, Annamária and Péter, Mária and Balogh, Gábor and Vizler, Csaba and Szente, Lajos and Vigh, László}, doi = {10.3390/cells9040951}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {9}, unique-id = {31319639}, year = {2020}, eissn = {2073-4409}, orcid-numbers = {Crul, Tim/0000-0002-6053-7016} } @article{MTMT:31665750, title = {Miért csillapított a stresszválasz az öregedés során, avagy a dajkafehérje expresszió és a membrán-fluiditás kapcsolata}, url = {https://m2.mtmt.hu/api/publication/31665750}, author = {Benkő, Sándor and Balogh, Gábor and Péter, Mária and Török, Zsolt and Gombos, Imre and Glatz, Attila and Horváth, Ibolya and Vigh, László}, journal-iso = {IDŐSGYÓGYÁSZAT}, journal = {IDŐSGYÓGYÁSZAT}, volume = {3}, unique-id = {31665750}, issn = {2498-8057}, year = {2018}, pages = {42-47}, orcid-numbers = {Benkő, Sándor/0000-0002-9379-8503} } @article{MTMT:30385388, title = {Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis}, url = {https://m2.mtmt.hu/api/publication/30385388}, author = {Márton, Judit and Péter, Mária and Balogh, Gábor and Bódi, Beáta and Vida, András and Szántó, Magdolna and Bojcsuk, Dóra and Jankó, Laura and Bhattoa Harjit, Pál and Gombos, Imre and Uray (Davis), Karen L. and Horváth, Ibolya and Török, Zsolt and Bálint, Bálint László and Papp, Zoltán and Vigh, László and Bay, Péter}, doi = {10.1016/j.bbalip.2018.07.013}, journal-iso = {BBA-MOL CELL BIOL L}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS}, volume = {1863}, unique-id = {30385388}, issn = {1388-1981}, abstract = {There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of PARP2 induced characteristic changes in the lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle. Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone, an anabolic steroid. Thus, skeletal muscle fibers in PARP2(-/-) mice were stronger compared to those of their wild-type littermates. In addition, we detected changes in the dynamics of the cell membrane, suggesting that lipidome changes also affect the biophysical characteristics of the cell membrane. In in silico and wet chemistry studies, we identified lipid species that can decrease the expression of PARP2 and potentially phenocopy the genetic abruption of PARP2, including artificial steroids. In view of these observations, we propose a new role for PARP2 as a lipid-modulated regulator of lipid metabolism.}, year = {2018}, eissn = {1879-2618}, pages = {1399-1412}, orcid-numbers = {Bojcsuk, Dóra/0000-0001-5091-7237; Bhattoa Harjit, Pál/0000-0002-4909-0065; Bálint, Bálint László/0000-0002-6163-7190} } @article{MTMT:3411899, title = {Chemotherapy induced PRL3 expression promotes cancer growth via plasma membrane remodeling and specific alterations of caveolae-associated signaling}, url = {https://m2.mtmt.hu/api/publication/3411899}, author = {Csoboz, Bálint and Gombos, Imre and Tátrai, Enikő and Tóvári, József and L. Kiss, Anna and Horváth, Ibolya and Vigh, László}, doi = {10.1186/s12964-018-0264-8}, journal-iso = {CELL COMM SIGN}, journal = {CELL COMMUNICATION AND SIGNALING}, volume = {16}, unique-id = {3411899}, issn = {1478-811X}, abstract = {BACKGROUND: The outcome of cancer therapy is greatly defined by the ability of a tumor cell to evade treatment and re-establish its bulk mass after medical interventions. Consequently, there is an urgent need for the characterization of molecules affecting tumor reoccurrence. The phosphatase of regenerating liver 3 (PRL3) protein was recently emerged among the targets that could affect such a phenomenon. METHODS: The expression induction of PRL3 in melanoma cells treated with chemotherapeutic agents was assessed by western blotting. The effect of PRL3 expression on cancer growth was investigated both in vitro and in vivo. The association of PRL3 with the caveolae structures of the plasma membrane was analyzed by detergent free raft purification. The effect of PRL3 expression on the membrane organization was assayed by electron microscopy and by membrane biophysical measurements. Purification of the plasma membrane fraction and co-immunoprecipitation were used to evaluate the altered protein composition of the plasma membrane upon PRL3 expression. RESULTS: Here, we identified PRL3 as a genotoxic stress-induced oncogene whose expression is significantly increased by the presence of classical antitumor therapeutics. Furthermore, we successfully connected the presence of this oncogene with increased tumor growth, which implies that tumor cells can utilize PRL3 effects as a survival strategy. We further demonstrated the molecular mechanism that is connected with the pro-growth action of PRL3, which is closely associated with its localization to the caveolae-type lipid raft compartment of the plasma membrane. In our study, PRL3 was associated with distinct changes in the plasma membrane structure and in the caveolar proteome, such as the dephosphorylation of integrin beta1 at Thr788/Thr789 and the increased partitioning of Rac1 to the plasma membrane. These alterations at the plasma membrane were further associated with the elevation of cyclin D1 in the nucleus. CONCLUSIONS: This study identifies PRL3 as an oncogene upregulated in cancer cells upon exposure to anticancer therapeutics. Furthermore, this work contributes to the existing knowledge on PRL3 function by characterizing its association with the caveolae-like domains of the plasma membrane and their resident proteins.}, year = {2018}, eissn = {1478-811X}, orcid-numbers = {Tátrai, Enikő/0000-0001-9778-2077; Tóvári, József/0000-0002-5543-3204} } @article{MTMT:3357955, title = {Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness}, url = {https://m2.mtmt.hu/api/publication/3357955}, author = {Mikó, Edit and Vida, András and Kovács, Tünde and Ujlaki, Gyula and Trencsényi, György and Márton, Judit and Sári, Zsanett Mercédesz and Kovács, Patrik Bence and Boratkó, Anita and Hujber, Zoltán and Csonka, Tamás and Antal-Szalmás, Péter and Watanabe, M and Gombos, Imre and Csoka, B and Kiss, Borbála Katalin and Vigh, László and Szabó, Judit and Méhes, Gábor and Sebestyén, Anna and Goedert, JJ and Bay, Péter}, doi = {10.1016/j.bbabio.2018.04.002}, journal-iso = {BBA-BIOENERGETICS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS}, volume = {1859}, unique-id = {3357955}, issn = {0005-2728}, abstract = {Our study aimed at finding a mechanistic relationship between the gut microbiome and breast cancer. Breast cancer cells are not in direct contact with these microbes, but disease could be influenced by bacterial metabolites including secondary bile acids that are exclusively synthesized by the microbiome and known to enter the human circulation. In murine and bench experiments, a secondary bile acid, lithocholic acid (LCA) in concentrations corresponding to its tissue reference concentrations (< 1 mu M), reduced cancer cell proliferation (by 10-20%) and VEGF production (by 37%), aggressiveness and metastatic potential of primary tumors through inducing mesenchymal-to-epithelial transition, increased antitumor immune response, OXPHOS and the TCA cycle. Part of these effects was due to activation of TGR5 by LCA. Early stage breast cancer patients, versus control women, had reduced serum LCA levels, reduced chenodeoxycholic acid to LCA ratio, and reduced abundance of the baiH (7 alpha/beta-hydroxysteroid dehydroxylase, the key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial generation of LCA in early breast cancer.}, keywords = {RISK; PATHWAYS; LIVER; MALIGNANCY; GUT; breast cancer; Antibiotic use; lithocholic acid; PROSTATE-CANCER; microbiome; Intestinal microbiota; Biochemistry & Molecular Biology; Endothelial-mesenchymal transition; OXPHOS; BILE-ACIDS}, year = {2018}, eissn = {1879-2650}, pages = {958-974}, orcid-numbers = {Trencsényi, György/0000-0001-6456-6212; Sebestyén, Anna/0000-0001-8814-4794} } @article{MTMT:3305696, title = {Mild heat induces a distinct "eustress" response in Chinese Hamster Ovary cells but does not induce heat shock protein synthesis}, url = {https://m2.mtmt.hu/api/publication/3305696}, author = {Peksel, Begüm and Gombos, Imre and Péter, Mária and Vígh, László Jr. and Tiszlavicz, Ádám and Brameshuber, M and Balogh, Gábor and Schutz, GJ and Horváth, Ibolya and Vigh, László and Török, Zsolt}, doi = {10.1038/s41598-017-15821-8}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {7}, unique-id = {3305696}, issn = {2045-2322}, abstract = {The current research on cellular heat stress management focuses on the roles of heat shock proteins (HSPs) and the proteostasis network under severe stress conditions. The mild, fever-type stress and the maintenance of membrane homeostasis are less well understood. Herein, we characterized the acute effect of mild, fever-range heat shock on membrane organization, and HSP synthesis and localization in two mammalian cell lines, to delineate the role of membranes in the sensing and adaptation to heat. A multidisciplinary approach combining ultrasensitive fluorescence microscopy and lipidomics revealed the molecular details of novel cellular "eustress", when cells adapt to mild heat by maintaining membrane homeostasis, activating lipid remodeling, and redistributing chaperone proteins. Notably, this leads to acquired thermotolerance in the complete absence of the induction of HSPs. At higher temperatures, additional defense mechanisms are activated, including elevated expression of molecular chaperones, contributing to an extended stress memory and acquired thermotolerance.}, keywords = {LOCALIZATION; PLASMA-MEMBRANE; ACTIVATION; ESCHERICHIA-COLI; GPI-ANCHORED PROTEINS; INDUCED APOPTOSIS; Hsp70; THERMOTOLERANCE; PHOSPHATIDIC-ACID; STRESS-PROTEINS}, year = {2017}, eissn = {2045-2322} } @article{MTMT:3200680, title = {Metabolic crosstalk between membrane and storage lipids facilitates heat stress management in Schizosaccharomyces pombe.}, url = {https://m2.mtmt.hu/api/publication/3200680}, author = {Péter, Mária and Glatz, Attila and Gudmann, Péter and Gombos, Imre and Török, Zsolt and Horváth, Ibolya and Vigh, László and Balogh, Gábor}, doi = {10.1371/journal.pone.0173739}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {12}, unique-id = {3200680}, issn = {1932-6203}, abstract = {Cell membranes actively participate in stress sensing and signalling. Here we present the first in-depth lipidomic analysis to characterize alterations in the fission yeast Schizosaccharomyces pombe in response to mild heat stress (HS). The lipidome was assessed by a simple one-step methanolic extraction. Genetic manipulations that altered triglyceride (TG) content in the absence or presence of HS gave rise to distinct lipidomic fingerprints for S. pombe. Cells unable to produce TG demonstrated long-lasting growth arrest and enhanced signalling lipid generation. Our results reveal that metabolic crosstalk between membrane and storage lipids facilitates homeostatic maintenance of the membrane physical/chemical state that resists negative effects on cell growth and viability in response to HS. We propose a novel stress adaptation mechanism in which heat-induced TG synthesis contributes to membrane rigidization by accommodating unsaturated fatty acids of structural lipids, enabling their replacement by newly synthesized saturated fatty acids.}, year = {2017}, eissn = {1932-6203} }