@article{MTMT:34797924, title = {Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability}, url = {https://m2.mtmt.hu/api/publication/34797924}, author = {Hudhud, Lina and Kovács-Rozmer, Katalin and Kecskés, Angéla and Pohóczky, Krisztina and Bencze, Noémi and Buzás, Krisztina and Szőke, Éva and Helyes, Zsuzsanna}, doi = {10.3390/ijms25073760}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34797924}, issn = {1661-6596}, abstract = {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.}, keywords = {CAPSAICIN; TRPV1; Cell viability; mustard oil; TRPA1; Osteosarcoma; RNAscope in situ hybridization; radioactive 45Ca2+ uptake}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Pohóczky, Krisztina/0000-0003-0385-5162; Buzás, Krisztina/0000-0001-8933-2033} } @article{MTMT:34377785, title = {Hemokinin-1 is a mediator of chronic restraint stress-induced pain}, url = {https://m2.mtmt.hu/api/publication/34377785}, author = {Borbély, Éva and Kecskés, Angéla and Kun, József and Kepe, Eszter and Fülöp, Barbara and Kovács-Rozmer, Katalin and Scheich, Bálint and Dobolyiné Renner, Éva and Palkovits, Miklós and Helyes, Zsuzsanna}, doi = {10.1038/s41598-023-46402-7}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34377785}, issn = {2045-2322}, abstract = {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.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Borbély, Éva/0000-0002-1234-4391; Palkovits, Miklós/0000-0003-0578-0387} } @article{MTMT:33826932, title = {Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice}, url = {https://m2.mtmt.hu/api/publication/33826932}, author = {Ngoc, Khai Huynh and Kecskés, Angéla and Kepe, Eszter and Nabi, Liza and Keeble, Julie and Borbély, Éva and Helyes, Zsuzsanna}, doi = {10.1016/j.euroneuro.2023.04.017}, journal-iso = {EUR NEUROPSYCHOPHARM}, journal = {EUROPEAN NEUROPSYCHOPHARMACOLOGY}, volume = {73}, unique-id = {33826932}, issn = {0924-977X}, abstract = {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.}, keywords = {TRPV1; DEPRESSION; Supramammillary nucleus; AMG9810; Glutamatergic neuron}, year = {2023}, eissn = {1873-7862}, pages = {96-107}, orcid-numbers = {Borbély, Éva/0000-0002-1234-4391} } @article{MTMT:33788849, title = {TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy}, url = {https://m2.mtmt.hu/api/publication/33788849}, author = {Mundrucz, Laura and Kecskés, Angéla and Henn-Mike, Nóra and Kóbor, Péter and Buzás, Péter and Vennekens, Rudi and Kecskés, Miklós}, doi = {10.1186/s12915-023-01604-3}, journal-iso = {BMC BIOL}, journal = {BMC BIOLOGY}, volume = {21}, unique-id = {33788849}, issn = {1741-7007}, abstract = {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.}, keywords = {EPILEPSY; ion channel; mossy cell; TRPM4}, year = {2023}, eissn = {1741-7007}, orcid-numbers = {Buzás, Péter/0000-0002-4390-3360} } @article{MTMT:33553718, title = {17β-estradiol does not have a direct effect on the function of striatal cholinergic interneurons in adult mice in vitro}, url = {https://m2.mtmt.hu/api/publication/33553718}, author = {Kövesdi, Erzsébet and Udvarácz, Ildikó and Kecskés, Angéla and Szőcs, Szilárd and Farkas, Szidónia and Faludi, Péter Béla and Jánosi, Tibor Zoltán and Ábrahám, István and Kovács, Gergely}, doi = {10.3389/fendo.2022.993552}, journal-iso = {FRONT ENDOCRINOL}, journal = {FRONTIERS IN ENDOCRINOLOGY}, volume = {13}, unique-id = {33553718}, issn = {1664-2392}, abstract = {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.}, year = {2023}, eissn = {1664-2392} } @article{MTMT:33287590, title = {The triple function of the capsaicin-sensitive sensory neurons: In memoriam János Szolcsányi}, url = {https://m2.mtmt.hu/api/publication/33287590}, author = {Pintér, Erika and Helyes, Zsuzsanna and Szőke, Éva and Bölcskei, Kata and Kecskés, Angéla and Pethő, Gábor}, doi = {10.1080/23328940.2022.2147388}, journal-iso = {TEMPERATURE}, journal = {TEMPERATURE}, volume = {10}, unique-id = {33287590}, issn = {2332-8940}, year = {2023}, eissn = {2332-8959}, pages = {13-34}, orcid-numbers = {Pintér, Erika/0000-0001-9898-632X} } @misc{MTMT:34044912, title = {Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy}, url = {https://m2.mtmt.hu/api/publication/34044912}, author = {Mundrucz, Laura and Kecskés, Angéla and Henn-Mike, Nóra and Kobor, Peter and Buzas, Peter and Vennekens, Rudi and Kecskes, Miklos}, unique-id = {34044912}, abstract = {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.}, year = {2022} } @article{MTMT:32819187, title = {Mossy cells of the dentate gyrus : Drivers or inhibitors of epileptic seizures?}, url = {https://m2.mtmt.hu/api/publication/32819187}, author = {Kecskés, Angéla and Czéh, Boldizsár and Kecskés, Miklós}, doi = {10.1016/j.bbamcr.2022.119279}, journal-iso = {BBA-MOL CELL RES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH}, volume = {1869}, unique-id = {32819187}, issn = {0167-4889}, abstract = {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.}, keywords = {hippocampus; EPILEPSY; dentate gyrus; granule cell; mossy cell}, year = {2022}, eissn = {1879-2596} } @article{MTMT:32674506, title = {Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability}, url = {https://m2.mtmt.hu/api/publication/32674506}, author = {Hudhud, Lina and Chisholm, D.R. and Whiting, A. and Steib, Anita and Pohóczky, Krisztina and Kecskés, Angéla and Szőke, Éva and Helyes, Zsuzsanna}, doi = {10.3390/molecules27030977}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {27}, unique-id = {32674506}, issn = {1420-3049}, year = {2022}, eissn = {1420-3049}, orcid-numbers = {Pohóczky, Krisztina/0000-0003-0385-5162} } @article{MTMT:32665502, title = {Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma}, url = {https://m2.mtmt.hu/api/publication/32665502}, author = {Kiss, Fruzsina and Kormos, Viktória and Szőke, Éva and Kecskés, Angéla and Tóth, Norbert and Steib, Anita and Szállási, Árpád and Scheich, Bálint and Gaszner, Balázs and Kun, József and Fülöp, Gábor and Pohóczky, Krisztina and Helyes, Zsuzsanna}, doi = {10.3390/ijms23031921}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {32665502}, issn = {1661-6596}, abstract = {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.}, keywords = {CAPSAICIN; TRPV1; Cell viability; TRPA1; Oral squamous cell carcinoma; AITC; RNAscope; diagnostic and prognostic biomarker; radioactive 45Ca2+ uptake; ATP-based luminescence}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Kiss, Fruzsina/0000-0001-9020-1567; Gaszner, Balázs/0000-0003-2830-2732; Pohóczky, Krisztina/0000-0003-0385-5162} }