Találati lista | Tudóstér

001-es BibID:	BIBFORM122715
035-os BibID:	(Scopus)85193054873 (WOS)001222011000001
Első szerző:	Kunka Árpád (arc-, állcsont- és szájsebész)
Cím:	TRPA1 up-regulation mediates oxidative stress in a pulpitis model in vitro / Árpád Kunka, Erika Lisztes, Judit Bohács, Márk Racskó, Balázs Kelemen, Gabriella Kovalecz, Etelka D. Tóth, Csaba Hegedűs, Kinga Bágyi, Rita Marincsák, Balázs István Tóth
Dátum:	2024
ISSN:	0007-1188
Megjegyzések:	Background and Purpose: Pulpitis is associated with tooth hypersensitivity and results in pulpal damage. Thermosensitive transient receptor potential (TRP) ion channels expressed in the dental pulp may be key transducers of inflammation and nociception. We aimed at investigating the expression and role of thermo-TRPs in primary human dental pulp cells (hDPCs) in normal and inflammatory conditions. Experimental Approach: Inflammatory conditions were induced in hDPC cultures by applying polyinosinic:polycytidylic acid (poly(I:C)). Gene expression and pro-inflammatory cytokine release were measured by RT-qPCR and ELISA. Functions of TRPA1 channels were investigated by monitoring changes in intracellular Ca2+ concentration. Mitochondrial superoxide production was measured using a fluorescent substrate. Cellular viability was assessed by measuring the activity of mitochondrial dehydrogenases and cytoplasmic esterases. TRPA1 activity was modified by agonists, antagonists, and gene silencing. Key Results: Transcripts of TRPV1, TRPV2, TRPV4, TRPC5, and TRPA1 were highly expressed in control hDPCs, whereas TRPV3, TRPM2, and TRPM3 expressions were much lower, and TRPM8 was not detected. Poly(I:C) markedly up-regulated TRPA1 but not other thermo-TRPs. TRPA1 agonist-induced Ca2+ signals were highly potentiated in inflammatory conditions. Poly(I:C)-treated cells displayed increased Ca2+ responses to H2O2, which was abolished by TRPA1 antagonists. Inflammatory conditions induced oxidative stress, stimulated mitochondrial superoxide production, resulted in mitochondrial damage, and decreased cellular viability of hDPCs. This inflammatory cellular damage was partly prevented by the co-application of TRPA1 antagonist or TRPA1 silencing. Conclusion and Implications: Pharmacological blockade of TRPA1 channels may be a promising therapeutic approach to alleviate pulpitis and inflammation-associated pulpal damage. ? 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk dental pulp endodontics immunopharmacology inflammation reactive oxygen species transient receptor potential channels TRPA1
Megjelenés:	British Journal Of Pharmacology. - 181 : 17 (2024), p. 3246-3262. -
További szerzők:	Lisztes Erika (1986-) (élettanász) Bohács Judit (1993-) (fogorvos) Racskó Márk (1991-) (molekuláris biológus) Kelemen Balázs (1992-) (biológus) Kovalecz Gabriella (1973-) (fogszakorvos) D. Tóth Etelka (1975-) (fogszakorvos) Hegedűs Csaba (1953-) (fogszakorvos) Bágyi Kinga (1971-) (fogszakorvos) Marincsák Rita (1979-) (fogszakorvos) Tóth István Balázs (1978-) (élettanász)
Pályázati támogatás:	EFOP-3.6.1-16-2016-00022 EFOP GINOP2.3.2-15-2016-00050 GINOP ÚNKP-21-5-DE-491 ÚNKP ÚNKP-22-3-IDE-324 ÚNKP ÚNKP-23-3-II-DE-430 ÚNKP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

001-es BibID:	BIBFORM118970
035-os BibID:	(Scopus)85193054873 (WoS)001222011000001
Első szerző:	Kunka Árpád (arc-, állcsont- és szájsebész)
Cím:	TRPA1 upregulation mediates oxidative stress in a pulpitis model in vitro / Árpád Kunka, Erika Lisztes, Judit Bohács, Márk Racskó, Balázs Kelemen, Gabriella Kovalecz, Etelka D. Tóth, Csaba Hegedűs, Kinga Bágyi, Rita Marincsák, Balázs István Tóth
Dátum:	2024
ISSN:	0007-1188
Megjegyzések:	BACKGROUND AND PURPOSE Pulpitis is associated with tooth hypersensitivity and results in pulpal damage. Thermosensitive transient receptor potential (TRP) ion channels expressed in the dental pulp may be key transducers of inflammation and nociception. We aimed at investigating the expression and role of thermo-TRPs in primary human dental pulp cells (hDPCs) in normal and inflammatory conditions. EXPERIMENTAL APPROACH Inflammatory conditions were induced in hDPC cultures by applying polyinosinic:polycytidylic acid (poly(I:C)). Gene expression and proinflammatory cytokine-release were measured by RT-qPCR and ELISA. Function of TRPA1 was investigated by monitoring changes in intracellular Ca2+ concentration. Mitochondrial superoxide production was measured using a fluorescent substrate and cellular viability was assessed by measuring the activity of mitochondrial dehydrogenases and cytoplasmic esterases. TRPA1 activity was manipulated by agonists, antagonists, and gene silencing. KEY RESULTS The transcripts of TRPV1, TRPV2, TRPV4, TRPC5, and TRPA1 were highly expressed in control hDPCs, whereas TRPV3, TRPM2, and TRPM3 expressions were much lower, and TRPM8 was not detected. Poly(I:C) markedly upregulated TRPA1 but not other thermo-TRPs. TRPA1 agonist-induced Ca2+ signals were highly potentiated in inflammatory conditions. Poly(I:C)-treated cells displayed increased Ca2+ responses to H2O2 which was abolished by TRPA1 antagonism. Inflammatory conditions induced oxidative stress, stimulated mitochondrial superoxide production, resulted in mitochondrial damage, and decreased cellular viability of hDPCs. This inflammatory cellular damage was partially prevented by the co-application of TRPA1 antagonist or TRPA1 silencing. CONCLUSION AND IMPLICATIONS The pharmacological blockade of TRPA1 may be a promising therapeutic approach to alleviate pulpitis and inflammation-associated pulpal damage.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Immunopharmacology Inflammation Transient Receptor Potential Channels TRPA1 Dental Pulp Reactive Oxygen Species Endodontics
Megjelenés:	British Journal of Pharmacology. - 181 : 17 (2024), p. 3246-3262. -
További szerzők:	Lisztes Erika (1986-) (élettanász) Bohács Judit (1993-) (fogorvos) Racskó Márk (1991-) (molekuláris biológus) Kelemen Balázs (1992-) (biológus) Kovalecz Gabriella (1973-) (fogszakorvos) D. Tóth Etelka (1975-) (fogszakorvos) Hegedűs Csaba (1953-) (fogszakorvos) Bágyi Kinga (1971-) (fogszakorvos) Marincsák Rita (1979-) (fogszakorvos) Tóth István Balázs (1978-) (élettanász)
Pályázati támogatás:	134725 OTKA 134791 OTKA EFOP-3.6.1-16-2016-00022 EFOP GINOP-2.3.2-15-2016-00050 GINOP ÚNKP-22-3-I-DE-324 Egyéb ÚNKP-21-5-DE-491 Egyéb János Bolyai Research Scholarship of the Hungarian Academy of Sciences Egyéb
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
Borító:
Saját polcon:

001-es BibID:	BIBFORM119089
Első szerző:	Tóth István Balázs (élettanász)
Cím:	Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants / Balázs István Tóth, Bahar Bazeli, Annelies Janssens, Erika Lisztes, Márk Racskó, Balázs Kelemen, Mihály Herczeg, Tamás Milán Nagy, Katalin E. Kövér, Argha Mitra, Attila Borics, Tamás Bíró, Thomas Voets
Dátum:	2024
ISSN:	2050-084X
Megjegyzések:	Rapamycin (sirolimus), a macrolide compound isolated from the bacterium Streptomyces hygroscopicus, is widely used as oral medication for the prevention of transplant rejection and the treatment of lymphangioleiomyomatosis. It is also incorporated in coronary stent coatings to prevent restenosis and in topical preparations for the treatment of skin disorders. Rapamycin's in vivo activities are generally ascribed to its binding to the protein FKBP12, leading to potent inhibition of the mechanistic target of rapamycin kinase (mTOR) by the FKBP12-rapamycin complex. The specific rapamycin-induced interaction between domains from mTOR and FKBP12 is also frequently employed in cell biological research, for rapid chemically-induced protein dimerization strategies. Here we show that rapamycin activates TRPM8, a cation channel expressed in sensory nerve endings that serves as the primary cold sensor in mammals. Using a combination of electrophysiology, Saturation Transfer Triple-Difference (STTD) NMR spectroscopy and molecular docking-based targeted mutagenesis, we demonstrate that rapamycin directly binds to TRPM8. We identify a rapamycin-binding site in the groove between voltage sensor-like domain and the pore domain, distinct from the interaction sites of cooling agents and known TRPM8 agonists menthol and icilin. Related macrolide immunosuppressants act as partial TRPM8 agonists, competing with rapamycin for the same binding site. These findings identify a novel molecular target for rapamycin and provide new insights into the mechanisms of TRPM8 activation, which may assist in the development of therapies targeting this ion channel. Moreover, our findings also indicate that caution is needed when using molecular approaches based on rapamycin-induced dimerization to study ion channel regulation.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk TRPM8 Rapamycin Electrophysiology NMR spectroscopy Neuroscience
Megjelenés:	eLife. - 13 (2024). -
További szerzők:	Bazeli, Bahar Janssens, Annelies Lisztes Erika (1986-) (élettanász) Racskó Márk (1991-) (molekuláris biológus) Kelemen Balázs (1992-) (biológus) Herczeg Mihály (1979-) (vegyész, biológia-kémia tanár) Nagy Tamás Milán (1993-) (vegyész, nmr) Kövér Katalin, E. (1956-2023) (vegyész) Mitra, Argha Borics Attila Bíró Tamás (1968-) (élettanász) Voets, Thomas
Pályázati támogatás:	134725 OTKA 134791 OTKA 128368 OTKA 137924 OTKA GINOP-2.3.2-15-2016-00050 GINOP GINOP-2.3.3-15-2016-00004 GINOP GINOP-2.2.1-15-2017-00044 GINOP János Bolyai Research Scholarship Egyéb ÚNKP-22-3-I-DE-324 Egyéb ÚNKP-23-3-II-DE-430 Egyéb UNKP-22-4-I-DE-87 Egyéb ÚNKP-21-5-DE-491 Egyéb FWO; G0B9520N Egyéb FWO; G0B7620N Egyéb esearch Council of KU Leuven (C2-TRP) Egyéb Queen Elisabeth Medical Foundation for Neurosciences Egyéb EU's Horizon 2020 research and innovation program under grant agreement No. 739593 Egyéb
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
Borító:
Saját polcon: