TY - JOUR AU - Csoboz, Bálint AU - Gombos, Imre AU - Kóta, Zoltán AU - Dukic, Barbara AU - Klement, Éva AU - Varga-Zsíros, Vanda AU - Lipinszki, Zoltán AU - Páli, Tibor AU - Vigh, László AU - Török, Zsolt TI - The Small Heat Shock Protein, HSPB1, Interacts with and Modulates the Physical Structure of Membranes JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 13 SN - 1661-6596 DO - 10.3390/ijms23137317 UR - https://m2.mtmt.hu/api/publication/32930192 ID - 32930192 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Tiszlavicz, Ádám AU - Gombos, Imre AU - Péter, Mária AU - Hegedűs, Zoltán AU - Hunya, Ákos AU - Dukic, Barbara AU - Nagy, István AU - Peksel, Begüm AU - Balogh, Gábor AU - Horváth, Ibolya AU - Vigh, László AU - Török, Zsolt TI - Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells. JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 5 PG - 24 SN - 2227-9059 DO - 10.3390/biomedicines10051172 UR - https://m2.mtmt.hu/api/publication/32849807 ID - 32849807 N1 - Funding Agency and Grant Number: Hungarian Basic Research Fund [OTKA ANN 132280]; Eotvos Lorand Research Network Funding text: This research was funded by the Hungarian Basic Research Fund (OTKA ANN 132280) and Eotvos Lorand Research Network. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Pető, Ágota AU - Kósa, Dóra AU - Haimhoffer, Ádám AU - Siposné Fehér, Pálma AU - Ujhelyi, Zoltán AU - Sinka, Dávid AU - Fenyvesi, Ferenc AU - Váradi, Judit AU - Vecsernyés, Miklós AU - Gyöngyösi, Alexandra AU - Lekli, István AU - Szentesi, Péter AU - Marton, Annamária AU - Gombos, Imre AU - Dukic, Barbara AU - Vigh, László AU - Bácskay, Ildikó TI - Nicotinic Amidoxime Derivate BGP-15, Topical Dosage Formulation and Anti-Inflammatory Effect JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 13 PY - 2021 IS - 12 PG - 17 SN - 1999-4923 DO - 10.3390/pharmaceutics13122037 UR - https://m2.mtmt.hu/api/publication/32515212 ID - 32515212 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Crul, Tim AU - Csoboz, Bálint AU - Gombos, Imre AU - Marton, Annamária AU - Péter, Mária AU - Balogh, Gábor AU - Vizler, Csaba AU - Szente, Lajos AU - Vigh, László TI - Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 4 PG - 14 SN - 2073-4409 DO - 10.3390/cells9040951 UR - https://m2.mtmt.hu/api/publication/31319639 ID - 31319639 LA - English DB - MTMT ER - TY - JOUR AU - Benkő, Sándor AU - Balogh, Gábor AU - Péter, Mária AU - Török, Zsolt AU - Gombos, Imre AU - Glatz, Attila AU - Horváth, Ibolya AU - Vigh, László TI - Miért csillapított a stresszválasz az öregedés során, avagy a dajkafehérje expresszió és a membrán-fluiditás kapcsolata JF - IDŐSGYÓGYÁSZAT J2 - IDŐSGYÓGYÁSZAT VL - 3 PY - 2018 IS - 2 SP - 42 EP - 47 PG - 6 SN - 2498-8057 UR - https://m2.mtmt.hu/api/publication/31665750 ID - 31665750 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Márton, Judit AU - Péter, Mária AU - Balogh, Gábor AU - Bódi, Beáta AU - Vida, András AU - Szántó, Magdolna AU - Bojcsuk, Dóra AU - Jankó, Laura AU - Bhattoa Harjit, Pál AU - Gombos, Imre AU - Uray (Davis), Karen L. AU - Horváth, Ibolya AU - Török, Zsolt AU - Bálint, Bálint László AU - Papp, Zoltán AU - Vigh, László AU - Bay, Péter TI - Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS J2 - BBA-MOL CELL BIOL L VL - 1863 PY - 2018 IS - 11 SP - 1399 EP - 1412 PG - 14 SN - 1388-1981 DO - 10.1016/j.bbalip.2018.07.013 UR - https://m2.mtmt.hu/api/publication/30385388 ID - 30385388 N1 - Cited By :4 Export Date: 20 September 2022 CODEN: BBMLF AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Csoboz, Bálint AU - Gombos, Imre AU - Tátrai, Enikő AU - Tóvári, József AU - L. Kiss, Anna AU - Horváth, Ibolya AU - Vigh, László TI - Chemotherapy induced PRL3 expression promotes cancer growth via plasma membrane remodeling and specific alterations of caveolae-associated signaling JF - CELL COMMUNICATION AND SIGNALING J2 - CELL COMM SIGN VL - 16 PY - 2018 IS - 1 PG - 12 SN - 1478-811X DO - 10.1186/s12964-018-0264-8 UR - https://m2.mtmt.hu/api/publication/3411899 ID - 3411899 N1 - Funding Agency and Grant Number: Ministry for National Economy [GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00040] Funding text: This work was supported by the Ministry for National Economy (GINOP-2.3.2-15-2016-00001 and GINOP-2.3.2-15-2016-00040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari Krt. 62, Szeged, 6726, Hungary Department of Experimental Pharmacology, National Institute of Oncology, Budapest, 1094, Hungary Department of Anatomy, Histology and Embryology, Semmelweis University Budapest, Budapest, 1094, Hungary Cited By :1 Export Date: 8 February 2021 Correspondence Address: Csoboz, B.; Institute of Biochemistry, Temesvari Krt. 62, Hungary; email: csoboz.balint@brc.mta.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Mikó, Edit AU - Vida, András AU - Kovács, Tünde AU - Ujlaki, Gyula AU - Trencsényi, György AU - Márton, Judit AU - Sári, Zsanett Mercédesz AU - Kovács, Patrik Bence AU - Boratkó, Anita AU - Hujber, Zoltán AU - Csonka, Tamás AU - Antal-Szalmás, Péter AU - Watanabe, M AU - Gombos, Imre AU - Csoka, B AU - Kiss, Borbála Katalin AU - Vigh, László AU - Szabó, Judit AU - Méhes, Gábor AU - Sebestyén, Anna AU - Goedert, JJ AU - Bay, Péter TI - Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS J2 - BBA-BIOENERGETICS VL - 1859 PY - 2018 IS - 9 SP - 958 EP - 974 PG - 17 SN - 0005-2728 DO - 10.1016/j.bbabio.2018.04.002 UR - https://m2.mtmt.hu/api/publication/3357955 ID - 3357955 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Peksel, Begüm AU - Gombos, Imre AU - Péter, Mária AU - Vígh, László Jr. AU - Tiszlavicz, Ádám AU - Brameshuber, M AU - Balogh, Gábor AU - Schutz, GJ AU - Horváth, Ibolya AU - Vigh, László AU - Török, Zsolt TI - Mild heat induces a distinct "eustress" response in Chinese Hamster Ovary cells but does not induce heat shock protein synthesis JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 7 PY - 2017 PG - 12 SN - 2045-2322 DO - 10.1038/s41598-017-15821-8 UR - https://m2.mtmt.hu/api/publication/3305696 ID - 3305696 N1 - OA gold AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Péter, Mária AU - Glatz, Attila AU - Gudmann, Péter AU - Gombos, Imre AU - Török, Zsolt AU - Horváth, Ibolya AU - Vigh, László AU - Balogh, Gábor TI - Metabolic crosstalk between membrane and storage lipids facilitates heat stress management in Schizosaccharomyces pombe. JF - PLOS ONE J2 - PLOS ONE VL - 12 PY - 2017 IS - 3 PG - 22 SN - 1932-6203 DO - 10.1371/journal.pone.0173739 UR - https://m2.mtmt.hu/api/publication/3200680 ID - 3200680 N1 - Cited By :19 Export Date: 27 May 2021 CODEN: POLNC AB - 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. LA - English DB - MTMT ER -