TY - JOUR AU - Horváth, Ádám AU - Steib, Anita AU - Nehr-Majoros, Andrea Kinga AU - Kántás, Boglárka AU - Király, Ágnes AU - Racskó, Márk AU - Tóth, Balázs István AU - Szánti-Pintér, Eszter AU - Kudová, Eva AU - Skodáné Földes, Rita AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 9 PG - 13 SN - 1661-6596 DO - 10.3390/ijms25094637 UR - https://m2.mtmt.hu/api/publication/34822686 ID - 34822686 AB - The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions. LA - English DB - MTMT ER - TY - JOUR AU - Rumbus, Zoltán AU - Fekete, Kata AU - Kelava, Leonardo AU - Gardos, Bibor AU - Klonfar, Krisztian AU - Kéringer, Patrik AU - Pintér, Erika AU - Pákai, Eszter AU - Garami, András TI - Ammonium chloride-induced hypothermia is attenuated by transient receptor potential channel vanilloid-1, but augmented by ankyrin-1 in rodents JF - LIFE SCIENCES J2 - LIFE SCI VL - 346 PY - 2024 PG - 12 SN - 0024-3205 DO - 10.1016/j.lfs.2024.122633 UR - https://m2.mtmt.hu/api/publication/34804165 ID - 34804165 N1 - Export Date: 22 April 2024; CODEN: LIFSA AB - Systemic administration of ammonium chloride (NH4Cl), an acidifying agent used in human patients and experimental conditions, causes hypothermia in mice, however, the mechanisms of the thermoregulatory response to NH4Cl and whether it develops in other species remained unknown.We studied body temperature (Tb) changes in rats and mice induced by intraperitoneal administration of NH4Cl after blockade of transient receptor potential vanilloid-1 (TRPV1) or ankyrin-1 (TRPA1) channels.In rats, NH4Cl decreased Tb by 0.4-0.8°C (p < 0.05). The NH4Cl-induced hypothermia also developed in Trpv1 knockout (Trpv1-/-) and wild-type (Trpv1+/+) mice, however, the Tb drop was exaggerated in Trpv1-/- mice compared to Trpv1+/+ controls with maximal decreases of 4.0 vs. 2.1°C, respectively (p < 0.05). Pharmacological blockade of TRPV1 channels with AMG 517 augmented the hypothermic response to NH4Cl in genetically unmodified mice and rats (p < 0.05 for both). In contrast, when NH4Cl was infused to mice genetically lacking the TRPA1 channel, the hypothermic response was significantly attenuated compared to wild-type controls with maximal mean Tb difference of 1.0°C between the genotypes (p = 0.008). Pretreatment of rats with a TRPA1 antagonist (A967079) also attenuated the NH4Cl-induced Tb drop with a maximal difference of 0.7°C between the pretreatment groups (p = 0.003).TRPV1 channels limit, whereas TRPA1 channels exaggerate the development of NH4Cl-induced hypothermia in rats and mice, but other mechanisms are also involved. Our results warrant for regular Tb control and careful consideration of NH4Cl treatment in patients with TRPA1 and TRPV1 channel dysfunctions. LA - English DB - MTMT ER - TY - JOUR AU - Hudhud, Lina AU - Rozmer, Katalin AU - Kecskés, Angéla AU - Pohóczky, Krisztina AU - Bencze, Noémi AU - Buzás, Krisztina AU - Szőke, Éva AU - Helyes, Zsuzsanna TI - Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 7 PG - 13 SN - 1661-6596 DO - 10.3390/ijms25073760 UR - https://m2.mtmt.hu/api/publication/34797924 ID - 34797924 N1 - * Megosztott szerzőség AB - Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives. LA - English DB - MTMT ER - TY - PAT AU - Pintér, Erika AU - Botz, Lajos AU - Pozsgai, Gábor AU - László, Szabolcs AU - Wagner, Ödön TI - Low-dose, stable-release transdermal preparation and patch, and method for their production PY - 2024 UR - https://m2.mtmt.hu/api/publication/34792101 ID - 34792101 LA - English DB - MTMT ER - TY - JOUR AU - Tarjányi, Vera AU - Ménes, Ákos AU - Hamid, Leila AU - Kurucz, Andrea AU - Priksz, Dániel AU - Varga, Balázs AU - Gesztelyi, Rudolf AU - Kiss, Rita AU - Horváth, Ádám István AU - Szentes, Nikolett AU - Helyes, Zsuzsanna AU - Szilvássy, Zoltán AU - Bombicz, Mariann TI - Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis : Effects on Disease Progression and Inflammatory Biomarkers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 6 PG - 16 SN - 1661-6596 DO - 10.3390/ijms25063292 UR - https://m2.mtmt.hu/api/publication/34763932 ID - 34763932 N1 - Funding Agency and Grant Number: European Union; State of Hungary; University of Debrecen [GINOP-2.3.4-15-2016-00002]; Hungarian Research Network (Chronic Pain Research Group); National Research, Development and Innovation Office (PharmaLab) [RRF-2.3.1-21-2022-00015, TKP2021-EGA-13, OTKA-K 134214]; National Research, Development and Innovation Fund of Hungary [TKP2021-EGA-13, TKP2021-EGA-16]; European Union and the European Regional Development Fund; National Research, Development and Innovation Fund of Hungary under the TKP2021-EGA funding scheme [TKP2021-EGA-18] Funding text: The present research was supported by the European Union, the State of Hungary, and the University of Debrecen under grant number GINOP-2.3.4-15-2016-00002 (V.T., D.P., R.G., Z.H., B.V., A.K., R.K., Z.S., M.B.), the Hungarian Research Network (Chronic Pain Research Group; Z.H.), National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015; Z.H.), TKP2021-EGA-13 (Z.H.), and OTKA-K 134214 (Z.H.). Projects no. TKP2021-EGA-13 and TKP2021-EGA-16 have been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the EGA 13 and EGA 16 funding schemes. The project is co-financed by the European Union and the European Regional Development Fund. Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme. AB - Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund's adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility. CFA was injected into the plantar surface of one hind paw and the root of the tail on day 0, and the tail root injection was repeated on day 1. Flu vaccination was performed on day 1 or 7. Paw volume was measured by plethysmometry, mechanonociceptive threshold by dynamic plantar aesthesiometry, neutrophil myeloperoxidase (MPO) activity, and vascular leakage using in vivo optical imaging throughout the 21-day experiment. Inflammatory markers were determined by Western blot and histopathology. CFA-induced swelling, an increase in MPO activity, plasma extravasation in the tibiotarsal joint. Mechanical hyperalgesia of the hind paw was observed 3 days after the injection, which gradually decreased. Co-administration of the flu vaccine on day 7 but not on day 1 resulted in significantly increased heme oxygenase 1 (HO-1) expression. The influenza vaccination appears to have a limited impact on the progression and severity of the inflammatory response and associated pain. Nevertheless, delayed vaccination could alter the disease activity, as indicated by the findings from assessments of edema and inflammatory biomarkers. HO-1 may serve as a potential marker for the severity of inflammation, particularly in the case of delayed vaccination. However, further investigation is needed to fully understand the regulation and role of HO-1, a task that falls outside the scope of the current study. LA - English DB - MTMT ER - TY - JOUR AU - Márton, Rege Anna AU - Sebők, Csilla AU - Mackei, Máté AU - Tráj, Patrik AU - Vörösházi, Júlia AU - Kemény, Ágnes AU - Neogrády, Zsuzsa AU - Mátis, Gábor TI - Cecropin A: investigation of a host defense peptide with multifaceted immunomodulatory activity in a chicken hepatic cell culture JF - FRONTIERS IN VETERINARY SCIENCE J2 - FRONT VET SCI VL - 11 PY - 2024 PG - 10 SN - 2297-1769 DO - 10.3389/fvets.2024.1337677 UR - https://m2.mtmt.hu/api/publication/34718275 ID - 34718275 N1 - project no. RRF-2.3.1-21-2022-00001 has been implemented with the support provided by the Recovery and Resilience Facility (RRF), financed under the National Recovery Fund budget estimate, RRF-2.3.1-21 funding scheme. AB - IntroductionHost defense peptides (HDPs) are increasingly referred to as promising candidates for the reduction of the use of conventional antibiotics, thereby combating antibiotic resistance. As HDPs have been described to exert various immunomodulatory effects, cecropin A (CecA) appears to be a potent agent to influence the host inflammatory response.MethodsIn the present study, a chicken primary hepatocyte–non-parenchymal cell co-culture was used to investigate the putative immunomodulatory effects of CecA alone and in inflammatory conditions evoked by polyinosinic-polycytidylic acid (Poly I:C). To examine the viability of the cells, the extracellular lactate dehydrogenase (LDH) activity was determined by colorimetric assay. Inflammatory markers interleukin (IL)-8 and transforming growth factor-ß1 (TGF-ß1) were investigated using the ELISA method, whereas concentrations of IL-6, IL-10, and interferon-γ (IFN-γ) were assayed by Luminex xMAP technology. Extracellular H2O2 and malondialdehyde levels were measured by fluorometric and colorimetric methods, respectively.ResultsResults of the lower concentrations suggested the safe application of CecA; however, it might contribute to hepatic cell membrane damage at its higher concentrations. We also found that the peptide alleviated the inflammatory response, reflected by the decreased production of the pro-inflammatory IL-6, IL-8, and IFN-γ. In addition, CecA diminished the levels of anti-inflammatory IL-10 and TGF-ß1. The oxidative markers measured remained unchanged in most cases of CecA exposure.DiscussionCecA displayed a multifaceted immunomodulatory but not purely anti-inflammatory activity on the hepatic cells, and might be suggested to maintain the hepatic inflammatory homeostasis in Poly I:C-triggered immune response. To conclude, our study suggests that CecA might be a promising molecule for the development of new immunomodulatory antibiotic-substitutive agents in poultry medicine; however, there is still a lot to clarify regarding its cellular effects. LA - English DB - MTMT ER - TY - JOUR AU - Nehr-Majoros, Andrea Kinga AU - Erostyák, János AU - Fenyvesi, Éva AU - Szabó-Meleg, Edina AU - Szőcs, Levente AU - Sétáló, György (ifj.) AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Cyclodextrin derivatives decrease Transient Receptor Potential vanilloid 1 and Ankyrin 1 ion channel activation via altering the surrounding membrane microenvironment by cholesterol depletion JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 12 PY - 2024 PG - 13 SN - 2296-634X DO - 10.3389/fcell.2024.1334130 UR - https://m2.mtmt.hu/api/publication/34689825 ID - 34689825 AB - Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) are nonselective cation channels expressed in primary sensory neurons and several other non-neuronal structures such as immune cells, keratinocytes, and vascular smooth muscle cells. They play important roles in nociception, pain processing and their chanellopathies are associated with the development of several pathological conditions. They are located in cholesterol- and sphingolipid-rich membrane lipid raft regions serving as platforms to modulate their activations. We demonstrated earlier that disruption of these lipid rafts leads to decreased TRP channel activation and exerts analgesic effects. Cyclodextrins are macrocyclic molecules able to form host-guest complexes with cholesterol and deplete it from the membrane lipid rafts. The aim of this study was to investigate 8 structurally different (methylated and non-methylated) CD derivatives on cell viability, mitochondrial membrane potential, membrane composition and activation abilities of the TRPV1 and TRPA1 channels. We showed that non-methylated derivatives have preferable safety profiles compared to methylated ones. Furthermore, methylated derivatives reduced mitochondrial membrane potential. However, all investigated derivatives influence the ordered cell membrane structure depleting membrane cholesterol and inhibit the TRPV1 agonist capsaicin- and the TRPA1 agonist allyl isothiocyanate-induced Ca 2+− influx. This mechanism of action might provide novel perspectives for the development of peripherally acting analgesics via indirectly decreasing the generation and transmission of nociceptive signals. LA - English DB - MTMT ER - TY - GEN AU - Andrea, Kinga Nehr-Majoros AU - Bencze, Noémi AU - Payrits, Maja AU - Kemény, Ágnes AU - György, Sétáló Jr. AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Analgesic effects of cyclodextrin derivatives via modulation of Transient Receptor Potential Ankyrin 1 ion channel function PY - 2024 UR - https://m2.mtmt.hu/api/publication/34577002 ID - 34577002 LA - English DB - MTMT ER - TY - JOUR AU - Kaci, Hana AU - Dombi, Ágnes AU - Gömbös, Patrik AU - Szabó, András AU - Bakos, Éva AU - Laczka, Csilla AU - Poór, Miklós TI - Interaction of mycotoxins zearalenone, α-zearalenol, and β-zearalenol with cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, and 3A4) enzymes and organic anion transporting polypeptides (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) JF - TOXICOLOGY IN VITRO J2 - TOXICOL IN VITRO VL - 96 PY - 2024 PG - 8 SN - 0887-2333 DO - 10.1016/j.tiv.2024.105789 UR - https://m2.mtmt.hu/api/publication/34575448 ID - 34575448 LA - English DB - MTMT ER - TY - JOUR AU - Milicic, Milica AU - Gaszner, Balázs AU - Berta, Gergely AU - Pintér, Erika AU - Kormos, Viktória TI - The Lack of TRPA1 Ion Channel Does Not Affect the Chronic Stress-Induced Activation of the Locus Ceruleus JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 3 PG - 11 SN - 1661-6596 DO - 10.3390/ijms25031765 UR - https://m2.mtmt.hu/api/publication/34574198 ID - 34574198 N1 - Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, H-7624, Hungary Department of Anatomy, Medical School and Research Group for Mood Disorders, University of Pécs, Pécs, H-7624, Hungary Department of Medical Biology, Medical School, University of Pécs, Pécs, H-7624, Hungary Export Date: 19 February 2024 Correspondence Address: Kormos, V.; Department of Pharmacology and Pharmacotherapy, Hungary; email: viktoria.kormos@aok.pte.hu AB - We have previously proven the involvement of transient receptor potential ankyrin 1 (TRPA1) in stress adaptation. A lack of TRPA1 affects both urocortin 1 (member of the corticotropin-releasing hormone (CRH) family) content of the Edinger-Westphal nucleus. The noradrenergic locus ceruleus (LC) is also an important player in mood control. We aimed at investigating whether the TRPA1 is expressed in the LC, and to test if the response to chronic variable mild stress (CVMS) is affected by a lack of TRPA1. The TRPA1 expression was examined via RNAscope in situ hybridization. We investigated TRPA1 knockout and wildtype mice using the CVMS model of depression. Tyrosine hydroxylase (TH) and FOSB double immunofluorescence were used to test the functional neuromorphological changes in the LC. No TRPA1 expression was detected in the LC. The TH content was not affected by CVMS exposure. The CVMS-induced FOSB immunosignal did not co-localize with the TH neurons. TRPA1 is not expressed in the LC. A lack of functional TRPA1 receptor neither directly nor indirectly affects the TH content of LC neurons under CVMS. LA - English DB - MTMT ER -