TY - JOUR AU - Hudhud, Lina AU - Kovács-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 - JOUR AU - Borbély, Éva AU - Kecskés, Angéla AU - Kun, József AU - Kepe, Eszter AU - Fülöp, Barbara AU - Kovács-Rozmer, Katalin AU - Scheich, Bálint AU - Dobolyiné Renner, Éva AU - Palkovits, Miklós AU - Helyes, Zsuzsanna TI - Hemokinin-1 is a mediator of chronic restraint stress-induced pain JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 15 SN - 2045-2322 DO - 10.1038/s41598-023-46402-7 UR - https://m2.mtmt.hu/api/publication/34377785 ID - 34377785 N1 - * Megosztott szerzőség AB - The Tac4 gene-derived hemokinin-1 (HK-1) binds to the NK1 receptor, similarly to Substance P, and plays a role in acute stress reactions and pain transmission in mice. Here we investigated Tac4 mRNA expression in stress and pain-related regions and its involvement in chronic restraint stress-evoked behavioral changes and pain using Tac4 gene-deleted (Tac4-/-) mice compared to C57Bl/6 wildtypes (WT). Tac4 mRNA was detected by in situ hybridization RNAscope technique. Touch sensitivity was assessed by esthesiometry, cold tolerance by paw withdrawal latency from 0°C water. Anxiety was evaluated in the light-dark box (LDB) and open field test (OFT), depression-like behavior in the tail suspension test (TST). Adrenal and thymus weights were measured at the end of the experiment. We found abundant Tac4 expression in the hypothalamic-pituitary-adrenal axis, but Tac4 mRNA was also detected in the hippocampus, amygdala, somatosensory and piriform cortices in mice, and in the frontal regions and the amygdala in humans. In Tac4-/- mice of both sexes, stress-induced mechanical, but not cold hyperalgesia was significantly decreased compared to WTs. Stress-induced behavioral alterations were mild or absent in male WT animals, while significant changes of these parameters could be detected in females. Thymus weight decrease can be observed in both sexes. Higher baseline anxiety and depression-like behaviors were detected in male but not in female HK-1-deficient mice, highlighting the importance of investigating both sexes in preclinical studies. We provided the first evidence for the potent nociceptive and stress regulating effects of HK-1 in chronic restraint stress paradigm. Identification of its targets might open new perspectives for therapy of stress-induced pain. LA - English DB - MTMT ER - TY - JOUR AU - Ngoc, Khai Huynh AU - Kecskés, Angéla AU - Kepe, Eszter AU - Nabi, Liza AU - Keeble, Julie AU - Borbély, Éva AU - Helyes, Zsuzsanna TI - Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice JF - EUROPEAN NEUROPSYCHOPHARMACOLOGY J2 - EUR NEUROPSYCHOPHARM VL - 73 PY - 2023 SP - 96 EP - 107 PG - 12 SN - 0924-977X DO - 10.1016/j.euroneuro.2023.04.017 UR - https://m2.mtmt.hu/api/publication/33826932 ID - 33826932 N1 - * Megosztott szerzőség AB - The Transient Receptor Potential Vanilloid 1 (TRPV1) non-selective cation channel predominantly expressed in primary sensory neurons of the dorsal root and trigeminal ganglia mediates pain and neurogenic inflammation. TRPV1 mRNA and immunoreactivity were described in the central nervous system (CNS), but its precise expression pattern and function have not been clarified. Here we investigated Trpv1 mRNA expression in the mouse brain using ultrasensitive RNAScope in situ hybridization. The role of TRPV1 in anxiety, depression-like behaviors and memory functions was investigated by TRPV1-deficient mice and pharmacological antagonism by AMG9810. Trpv1 mRNA is selectively expressed in the supramammillary nucleus (SuM) co-localized with Vglut2 mRNA, but not with tyrosine hydroxylase immunopositivity demonstrating its presence in glutamatergic, but not dopaminergic neurons. TRPV1-deleted mice exhibited significantly reduced anxiety in the Light-Dark box and depression-like behaviors in the Forced Swim Test, but their performance in the Elevated Plus Maze as well as their spontaneous locomotor activity, memory and learning function in the Radial Arm Maze, Y-maze and Novel Object Recognition test were not different from WTs. AMG9810 (intraperitoneal injection 50 mg/kg) induced anti-depressant, but not anxiolytic effects. It is concluded that TRPV1 in the SuM might have functional relevance in mood regulation and TRPV1 antagonism could be a novel perspective for anti-depressant drugs. LA - English DB - MTMT ER - TY - JOUR AU - Mundrucz, Laura AU - Kecskés, Angéla AU - Henn-Mike, Nóra AU - Kóbor, Péter AU - Buzás, Péter AU - Vennekens, Rudi AU - Kecskés, Miklós TI - TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy JF - BMC BIOLOGY J2 - BMC BIOL VL - 21 PY - 2023 IS - 1 PG - 12 SN - 1741-7007 DO - 10.1186/s12915-023-01604-3 UR - https://m2.mtmt.hu/api/publication/33788849 ID - 33788849 N1 - * Megosztott szerzőség AB - Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients; however, the mechanisms leading to cellular death is unclear.Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated non-selective cation channel regulating diverse physiological functions of excitable cells. Here, we identified that TRPM4 is present in hilar mossy cells and regulates their intrinsic electrophysiological properties including spontaneous activity and action potential dynamics. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits.Our results provide evidence for the role of TRPM4 in MC excitability both in physiological and pathological conditions. LA - English DB - MTMT ER - TY - JOUR AU - Kövesdi, Erzsébet AU - Udvarácz, Ildikó AU - Kecskés, Angéla AU - Szőcs, Szilárd AU - Farkas, Szidónia AU - Faludi, Péter Béla AU - Jánosi, Tibor Zoltán AU - Ábrahám, István AU - Kovács, Gergely TI - 17β-estradiol does not have a direct effect on the function of striatal cholinergic interneurons in adult mice in vitro JF - FRONTIERS IN ENDOCRINOLOGY J2 - FRONT ENDOCRINOL VL - 13 PY - 2023 PG - 14 SN - 1664-2392 DO - 10.3389/fendo.2022.993552 UR - https://m2.mtmt.hu/api/publication/33553718 ID - 33553718 N1 - Institute of Physiology, Medical School, University of Pécs, Pécs, Hungary Centre for Neuroscience, Szentágothai Research Centre, Pécs, Hungary Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary Cited By :2 Export Date: 13 February 2024 Correspondence Address: Kovács, G.; Institute of Physiology, Hungary; email: gergely.kovacs@aok.pte.hu Chemicals/CAS: estradiol, 50-28-2 Tradenames: LSM710, Carl Zeiss, Germany Manufacturers: Carl Zeiss, Germany Funding details: 20017-1.2.1-NKP-2017-00002, KTIA_NAP_13-2014-0001 Funding details: European Commission, EC Funding details: Hungarian Scientific Research Fund, OTKA, 112807 Funding details: European Social Fund, ESF, EFOP 3.6.2-16-2017-00008, EFOP-3.6.1 Funding details: Pécsi Tudományegyetem, PTE, KA-2020-11, TKP2021-EGA-16 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: This work was supported by the Research Grant of Medical School, University of Pécs (KA-2020-11), the project TKP2021-EGA-16 that has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme, the Hungarian Scientific Research Fund (OTKA; 112807), the Hungarian Brain Research Program (KTIA_NAP_13-2014-0001, 20017-1.2.1-NKP-2017-00002), and the European Union and was co-financed by the European Social Fund under the following grants: EFOP-3.6.1.-16-2016-00004 (Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs), EFOP 3.6.2-16-2017-00008 (The Role of Neuro-inflammation in Neurodegeneration: From Molecules to Clinics). Acknowledgments Funding text 2: This work was supported by the Research Grant of Medical School, University of Pécs (KA-2020-11), the project TKP2021-EGA-16 that has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme, the Hungarian Scientific Research Fund (OTKA; 112807), the Hungarian Brain Research Program (KTIA_NAP_13-2014-0001, 20017-1.2.1-NKP-2017-00002), and the European Union and was co-financed by the European Social Fund under the following grants: EFOP-3.6.1.-16-2016-00004 (Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs), EFOP 3.6.2-16-2017-00008 (The Role of Neuro-inflammation in Neurodegeneration: From Molecules to Clinics). AB - The striatum is an essential component of the basal ganglia that is involved in motor control, action selection and motor learning. The pathophysiological changes of the striatum are present in several neurological and psychiatric disorder including Parkinson’s and Huntington’s diseases. The striatal cholinergic neurons are the main regulators of striatal microcircuitry. It has been demonstrated that estrogen exerts various effects on neuronal functions in dopaminergic and medium spiny neurons (MSN), however little is known about how the activity of cholinergic interneurons are influenced by estrogens. In this study we examined the acute effect of 17β-estradiol on the function of striatal cholinergic neurons in adult mice in vitro . We also tested the effect of estrus cycle and sex on the spontaneous activity of cholinergic interneurons in the striatum. Our RNAscope experiments showed that ERα, ERβ, and GPER1 receptor mRNAs are expressed in some striatal cholinergic neurons at a very low level. In cell-attached patch clamp experiments, we found that a high dose of 17β-estradiol (100 nM) affected the spontaneous firing rate of these neurons only in old males. Our findings did not demonstrate any acute effect of a low concentration of 17β-estradiol (100 pM) or show any association of estrus cycle or sex with the activity of striatal cholinergic neurons. Although estrogen did not induce changes in the intrinsic properties of neurons, indirect effects via modulation of the synaptic inputs of striatal cholinergic interneurons cannot be excluded. LA - English DB - MTMT ER - TY - JOUR AU - Pintér, Erika AU - Helyes, Zsuzsanna AU - Szőke, Éva AU - Bölcskei, Kata AU - Kecskés, Angéla AU - Pethő, Gábor TI - The triple function of the capsaicin-sensitive sensory neurons: In memoriam János Szolcsányi JF - TEMPERATURE J2 - TEMPERATURE VL - 10 PY - 2023 IS - 1 SP - 13 EP - 34 PG - 22 SN - 2332-8940 DO - 10.1080/23328940.2022.2147388 UR - https://m2.mtmt.hu/api/publication/33287590 ID - 33287590 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - GEN AU - Mundrucz, Laura AU - Kecskés, Angéla AU - Henn-Mike, Nóra AU - Kobor, Peter AU - Buzas, Peter AU - Vennekens, Rudi AU - Kecskes, Miklos TI - Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy PY - 2022 UR - https://m2.mtmt.hu/api/publication/34044912 ID - 34044912 AB - Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients, however the mechanisms leading to cellular death is unclear. One possible explanation for their sensitivity is linked to their specific ion channel composition. TRPM4 is a Ca2+-activated non-selective cation channel regulating diverse physiological function of excitable cells. Here, we identified that TRPM4 is present and functionally active in hilar mossy cells. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits in the chronic phase of TLE. LA - English DB - MTMT ER - TY - JOUR AU - Kecskés, Angéla AU - Czéh, Boldizsár AU - Kecskés, Miklós TI - Mossy cells of the dentate gyrus : Drivers or inhibitors of epileptic seizures? JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH J2 - BBA-MOL CELL RES VL - 1869 PY - 2022 IS - 9 PG - 6 SN - 0167-4889 DO - 10.1016/j.bbamcr.2022.119279 UR - https://m2.mtmt.hu/api/publication/32819187 ID - 32819187 AB - Mossy cells (MCs) are glutamatergic cells of the dentate gyrus with an important role in temporal lobe epilepsy. Under physiological conditions MCs can control both network excitations via direct synapses to granule cells and inhibition via connections to GABAergic interneurons innervating granule cells. In temporal lobe epilepsy mossy cell loss is one of the major hallmarks, but whether the surviving MCs drive or inhibit seizure initiation and generalization is still a debate. The aim of the present review is to summarize the latest findings on the role of mossy cells in healthy and overexcited hippocampus. LA - English DB - MTMT ER - TY - JOUR AU - Hudhud, Lina AU - Chisholm, D.R. AU - Whiting, A. AU - Steib, Anita AU - Pohóczky, Krisztina AU - Kecskés, Angéla AU - Szőke, Éva AU - Helyes, Zsuzsanna TI - Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 3 PG - 10 SN - 1420-3049 DO - 10.3390/molecules27030977 UR - https://m2.mtmt.hu/api/publication/32674506 ID - 32674506 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Fruzsina AU - Kormos, Viktória AU - Szőke, Éva AU - Kecskés, Angéla AU - Tóth, Norbert AU - Steib, Anita AU - Szállási, Árpád AU - Scheich, Bálint AU - Gaszner, Balázs AU - Kun, József AU - Fülöp, Gábor AU - Pohóczky, Krisztina AU - Helyes, Zsuzsanna TI - Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 3 PG - 14 SN - 1661-6596 DO - 10.3390/ijms23031921 UR - https://m2.mtmt.hu/api/publication/32665502 ID - 32665502 N1 - * Megosztott szerzőség AB - Oral squamous cell carcinoma (OSCC) is a common cancer with poor prognosis. Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) receptors are non-selective cation channels expressed on primary sensory neurons and epithelial and immune cells. TRPV1 mRNA and immunopositivity, as well as TRPA1-like immunoreactivity upregulation, were demonstrated in OSCC, but selectivity problems with the antibodies still raise questions and their functional relevance is unclear. Therefore, here, we investigated TRPA1 and TRPV1 expressions in OSCC and analyzed their functions. TRPA1 and TRPV1 mRNA were determined by RNAscope in situ hybridization and qPCR. Radioactive 45Ca2+ uptake and ATP-based luminescence indicating cell viability were measured in PE/CA-PJ41 cells in response to the TRPA1 agonist allyl-isothiocyanate (AITC) and TRPV1 agonist capsaicin to determine receptor function. Both TRPA1 and TRPV1 mRNA are expressed in the squamous epithelium of the human oral mucosa and in PE/CA-PJ41 cells, and their expressions are significantly upregulated in OSCC compared to healthy mucosa. TRPA1 and TRPV1 activation (100 µM AITC, 100 nM capsaicin) induced 45Ca2+-influx into PE/CA-PJ41 cells. Both AITC (10 nM–5 µM) and capsaicin (100 nM–45 µM) reduced cell viability, reaching significant decrease at 100 nM AITC and 45 µM capsaicin. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the OSCC and confirm the expression of TRPV1 channel. These channels are functionally active and might regulate cancer cell viability. LA - English DB - MTMT ER -