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 - Datki, Zsolt László AU - Oláh, Zita AU - Jánosi-Mózes, Emese AU - Szegedi, Viktor AU - Kálmán, János AU - Hunya, Ákos AU - Fülöp, Lívia AU - Tamano, Haruna AU - Takeda, Atsushi AU - Adlard, Paul A. AU - Bush, Ashley I. TI - Alzheimer risk factors age and female sex induce cortical Aβ aggregation by raising extracellular zinc [Alzheimer risk factors age and female sex induce cortical A beta aggregation by raising extracellular zinc] JF - MOLECULAR PSYCHIATRY J2 - MOL PSYCHIATR VL - 25 PY - 2020 IS - 11 SP - 2728 EP - 2741 PG - 14 SN - 1359-4184 DO - 10.1038/s41380-020-0800-y UR - https://m2.mtmt.hu/api/publication/31341681 ID - 31341681 AB - Aging and female sex are the major risk factors for Alzheimer's disease and its associated brain amyloid-beta (A beta) neuropathology, but the mechanisms mediating these risk factors remain uncertain. Evidence indicates that A beta aggregation by Zn(2+)released from glutamatergic neurons contributes to amyloid neuropathology, so we tested whether aging and sex adversely influences this neurophysiology. Using acute hippocampal slices, we found that extracellular Zn2+-elevation induced by high K(+)stimulation was significantly greater with older (65 weeks vs 10 weeks old) rats, and was exaggerated in females. This was driven by slower reuptake of extracellular Zn2+, which could be recapitulated by mitochondrial intoxication. Zn2+:A beta aggregates were toxic to the slices, but A beta alone was not. Accordingly, high K(+)caused synthetic human A beta added to the slices to form soluble oligomers as detected by bis-ANS, attaching to neurons and inducing toxicity, with older slices being more vulnerable. Age-dependent energy failure impairing Zn(2+)reuptake, and a higher maximal capacity for Zn(2+)release by females, could contribute to age and sex being major risk factors for Alzheimer's disease. LA - English DB - MTMT ER - TY - CHAP AU - Körmöczi, Tímea AU - Kovács, Orsolya AU - Sija, Éva AU - Hunya, Ákos AU - Samavati, Reza AU - Gáspár, Róbert AU - Institóris, László AU - Ilisz, István AU - Berkecz, Róbert ED - Ádám, Anna Adél ED - Ziegenheim, Szilveszter TI - Dizájner drogok és metabolitjaik az igazságügyi gyakorlatban T2 - XLII. Kémiai Előadói Napok - Előadásösszefoglalók PB - Magyar Kémikusok Egyesülete Csongrád Megyei Csoport CY - Szeged SN - 9786156018014 PY - 2019 SP - 73 EP - 77 PG - 5 UR - https://m2.mtmt.hu/api/publication/31619291 ID - 31619291 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Körmöczi, Tímea AU - Kovács, Orsolya AU - Sija, Éva AU - Hunya, Ákos AU - Samavati, Reza AU - Gáspár, Róbert AU - Institóris, László AU - Ilisz, István AU - Berkecz, Róbert ED - Alapi, Tünde ED - Ilisz, István TI - Analysis of designer drugs and their metabolites in blood and urine samples T2 - Proceedings of the 25th International Symposium on Analytical and Environmental Problems PB - University of Szeged CY - Szeged SN - 9789633067024 PY - 2019 SP - 80 EP - 80 PG - 1 UR - https://m2.mtmt.hu/api/publication/31619279 ID - 31619279 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Írisz AU - M.Tóth, Orsolya AU - Török, Zsolt AU - Varga, Dániel Péter AU - Menyhárt, Ákos AU - Frank, Rita AU - Hantosi, Dóra AU - Hunya, Ákos AU - Bari, Ferenc AU - Horváth, Ibolya AU - Vigh, László AU - Farkas, Eszter TI - The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization JF - BRITISH JOURNAL OF PHARMACOLOGY J2 - BR J PHARMACOL VL - 176 PY - 2019 IS - 9 SP - 1222 EP - 1234 PG - 13 SN - 0007-1188 DO - 10.1111/bph.14611 UR - https://m2.mtmt.hu/api/publication/30431480 ID - 30431480 N1 - Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary LipidArt Research and Development Ltd., Szeged, Hungary Export Date: 27 September 2019 CODEN: BJPCB Correspondence Address: Farkas, E.; Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of SzegedHungary; email: farkas.eszter.1@med.u-szeged.hu AB - A new class of heat shock protein co-inducer dihydropyridine derivatives devoid of calcium channel antagonist and vasodilator effects have been recently developed with the purpose to target neurodegeneration selectively. Here we set out to evaluate the action of one of these novel compounds LA1011 on neurovascular coupling in the ischemic rat cerebral cortex. As a reference, we applied nimodipine, a well-known calcium channel antagonist, vasodilator dihydropyridine compound.Rats (n=62) were treated with LA1011 or nimodipine, either by chronic, systemic (LA1011, 1 mg/kg b.w.), or acute, local administration (LA1011 and nimodipine, 100 μM). In the latter treatment group, global forebrain ischemia was induced in half of the animals by bilateral common carotid artery occlusion under isoflurane anesthesia. Functional hyperemia in the somatosensory cortex was created by mechanical stimulation of the contralateral whisker pad under alpha-chloralose anesthesia. Spreading depolarization (SD) events were elicited subsequently by 1 M KCl. Local field potential and cerebral blood flow (CBF) in the parietal somatosensory cortex were monitored by electrophysiology and laser Doppler flowmetry.LA1011 did not alter CBF, but intensified SD, presumably indicating the co-induction of heat shock proteins, and, perhaps an anti-inflammatory effect. Nimodipine attenuated evoked potentials and SD. In addition to the elevation of baseline CBF, nimodipine augmented hyperemia in response to both somatosensory stimulation and SD, particularly under ischemia. In conclusion, in contrast with CBF improvement achieved by nimodipine, LA1011 seems not to have discernible cerebrovascular effects, but may upregulate stress response. LA - English DB - MTMT ER - TY - JOUR AU - Kasza, Ágnes AU - Penke, Botond AU - Frank, Z AU - Bozsó, Zsolt AU - Szegedi, Viktor AU - Hunya, Ákos AU - Nemeth, K AU - Kozma, Gábor AU - Fülöp, Lívia TI - Studies for improving a rat model of Alzheimer's disease: ICV administration of well-characterized β-amyloid 1-42 oligomers induce dysfunction in spatial memory JF - MOLECULES J2 - MOLECULES VL - 22 PY - 2017 IS - 11 PG - 28 SN - 1420-3049 DO - 10.3390/molecules22112007 UR - https://m2.mtmt.hu/api/publication/3310819 ID - 3310819 N1 - N1 Funding details: GINOP-2.3.2-15-2016-00060 N1 Funding text: Acknowledgments: We are very grateful for László Siklós for the measurements of dendritic spine density. The authors express their thanks to Anita Kurunczi and Eszter Sipos for the studies on AMCA labeled Aβ fibrils. This work was supported by the EC Health Program “Memoload” (FP-7 project n◦ 201.159) and the Hungarian NKFIH research grant GINOP-2.3.2-15-2016-00060. LA - English DB - MTMT ER - TY - JOUR AU - Kasza, Ágnes AU - Hunya, Ákos AU - Frank, Z AU - Fülöp, Ferenc AU - Török, Zsolt AU - Balogh, Gábor AU - Sántha, Miklós AU - Bálind, Árpád AU - Bernáth, S AU - Blundell, KLIM AU - Prodromou, C AU - Horváth, Ibolya AU - Zeiler, H-J AU - Hooper, PL AU - Vigh, László AU - Penke, Botond TI - Dihydropyridine Derivatives Modulate Heat Shock Responses and have a Neuroprotective Effect in a Transgenic Mouse Model of Alzheimer's Disease JF - JOURNAL OF ALZHEIMER'S DISEASE J2 - J ALZHEIMERS DIS VL - 53 PY - 2016 IS - 2 SP - 557 EP - 571 PG - 15 SN - 1387-2877 DO - 10.3233/JAD-150860 UR - https://m2.mtmt.hu/api/publication/3099240 ID - 3099240 N1 - N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-25987808 N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-25987864 N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-25987869 N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-25987876 N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-25987882 N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-26158161 N1 Funding Details: 095605/Z11/Z, Wellcome Trust Megjegyzés-25987787 N1 Funding Details: 095605/Z11/Z, Wellcome Trust AB - Heat shock proteins (Hsps) have chaperone activity and play a pivotal role in the homeostasis of proteins by preventing misfolding, by clearing aggregated and damaged proteins from cells, and by maintaining proteins in an active state. Alzheimer's disease (AD) is thought to be caused by amyloid-β peptide that triggers tau hyperphosphorylation, which is neurotoxic. Although proteostasis capacity declines with age and facilitates the manifestation of neurodegenerative diseases such as AD, the upregulation of chaperones improves prognosis. Our research goal is to identify potent Hsp co-inducers that enhance protein homeostasis for the treatment of AD, especially 1,4-dihydropyridine derivatives optimized for their ability to modulate cellular stress responses. Based on favorable toxicological data and Hsp co-inducing activity, LA1011 was selected for the in vivo analysis of its neuroprotective effect in the APPxPS1 mouse model of AD. Here, we report that 6 months of LA1011 administration effectively improved the spatial learning and memory functions in wild type mice and eliminated neurodegeneration in double mutant mice. Furthermore, Hsp co-inducer therapy preserves the number of neurons, increases dendritic spine density, and reduces tau pathology and amyloid plaque formation in transgenic AD mice. In conclusion, the Hsp co-inducer LA1011 is neuroprotective and therefore is a potential pharmaceutical candidate for the therapy of neurodegenerative diseases, particularly AD. © 2016 - IOS Press and the authors. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Glatz, Attila AU - Pilbat, Ana Maria AU - Nemeth, GL AU - Kontár, Katalin AU - Jósvay, Katalin AU - Hunya, Ákos AU - Udvardy, Andor AU - Gombos, Imre AU - Péter, Mária AU - Balogh, Gábor AU - Horváth, Ibolya AU - Vigh, László AU - Török, Zsolt TI - Involvement of small heat shock proteins, trehalose, and lipids in the thermal stress management in Schizosaccharomyces pombe. JF - CELL STRESS & CHAPERONES J2 - CELL STRESS CHAPERON VL - 21 PY - 2016 IS - 2 SP - 327 EP - 338 PG - 12 SN - 1355-8145 DO - 10.1007/s12192-015-0662-4 UR - https://m2.mtmt.hu/api/publication/2990307 ID - 2990307 N1 - Export Date: 20 June 2019 CODEN: CSCHF Cited By :24 Export Date: 27 May 2021 CODEN: CSCHF Correspondence Address: Török, Z.; Institute of Biochemistry, Hungary; email: torok.zsolt@brc.mta.hu AB - Changes in the levels of three structurally and functionally different important thermoprotectant molecules, namely small heat shock proteins (sHsps), trehalose, and lipids, have been investigated upon heat shock in Schizosaccharomyces pombe. Both alpha-crystallin-type sHsps (Hsp15.8 and Hsp16) were induced after prolonged high-temperature treatment but with different kinetic profiles. The shsp null mutants display a weak, but significant, heat sensitivity indicating their importance in the thermal stress management. The heat induction of sHsps is different in wild type and in highly heat-sensitive trehalose-deficient (tps1Delta) cells; however, trehalose level did not show significant alteration in shsp mutants. The altered timing of trehalose accumulation and induction of sHsps suggest that the disaccharide might provide protection at the early stage of the heat stress while elevated amount of sHsps are required at the later phase. The cellular lipid compositions of two different temperature-adapted wild-type S. pombe cells are also altered according to the rule of homeoviscous adaptation, indicating their crucial role in adapting to the environmental temperature changes. Both Hsp15.8 and Hsp16 are able to bind to different lipids isolated from S. pombe, whose interaction might provide a powerful protection against heat-induced damages of the membranes. Our data suggest that all the three investigated thermoprotectant macromolecules play a pivotal role during the thermal stress management in the fission yeast. LA - English DB - MTMT ER - TY - THES AU - Hunya, Ákos TI - Physiological factors could enhance amyloid-beta toxicity PB - Szegedi Tudományegyetem (SZTE) PY - 2013 SP - 66 DO - 10.14232/phd.1674 UR - https://m2.mtmt.hu/api/publication/2856341 ID - 2856341 LA - English DB - MTMT ER - TY - JOUR AU - Crul, Tim AU - Crul-Tóth, Noémi AU - Piotto, S AU - Literáti-Nagy, Péter AU - Tory, K AU - Haldimann, P AU - Kalmar, B AU - Greensmith, L AU - Török, Zsolt AU - Balogh, Gábor AU - Gombos, Imre AU - Campana, F AU - Concilio, S AU - Gallyas, Ferenc AU - Nagy, G AU - Berente, Zoltán AU - Güngör, Burcin AU - Péter, Mária AU - Glatz, Attila AU - Hunya, Ákos AU - Literáti-Nagy, Zsuzsanna AU - Vígh, László Jr. AU - Hoogstra-Berends, F AU - Heeres, A AU - Kuipers, I AU - Loen, L AU - Seerden, JP AU - Zhang, D AU - Meijering, RA AU - Henning, RH AU - Brundel, BJ AU - Kampinga, HH AU - Korányi, László AU - Szilvássy, Zoltán AU - Mandl, József AU - Sümegi, Balázs AU - Febbraio, MA AU - Horváth, Ibolya AU - Hooper, PL AU - Vigh, László TI - Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness JF - CURRENT PHARMACEUTICAL DESIGN J2 - CURR PHARM DESIGN VL - 19 PY - 2013 IS - 3 SP - 309 EP - 346 PG - 38 SN - 1381-6128 DO - 10.2174/1381612811306030309 UR - https://m2.mtmt.hu/api/publication/2096112 ID - 2096112 AB - According to the "membrane sensor" hypothesis, the membranes physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy. LA - English DB - MTMT ER -