@article{MTMT:31604811, title = {A “keto-enol” plaque buster mechanism to diminish Alzheimer’s β-Amyloid burden}, url = {https://m2.mtmt.hu/api/publication/31604811}, author = {Oláh, Zoltán and László, Pecze and Éva, Kocsis and Viskolcz, Béla}, doi = {10.1016/j.bbrc.2020.07.086}, journal-iso = {BIOCHEM BIOPH RES CO}, journal = {BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS}, volume = {532}, unique-id = {31604811}, issn = {0006-291X}, year = {2020}, eissn = {1090-2104}, pages = {82-87} } @article{MTMT:3318960, title = {Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells}, url = {https://m2.mtmt.hu/api/publication/3318960}, author = {Nazıroğlu, M and Blum, W and Jósvay, Katalin and Çiğ, B and Henzi, T and Oláh, Zoltán and Vizler, Csaba and Schwaller, B and Pecze, László}, doi = {10.1016/j.redox.2017.10.009}, journal-iso = {REDOX BIOL}, journal = {REDOX BIOLOGY}, volume = {14}, unique-id = {3318960}, issn = {2213-2317}, abstract = {Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca2+ signals in breast and prostate cancer cell lines. The effect of menthol (50–500 µM) was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8). However, the intensity of menthol-evoked Ca2+ signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway. Menthol-evoked Ca2+ signals were analyzed in detail in Du 145 prostate cancer cells, as well as in CRISPR/Cas9 TRPM8-knockout Du 145 cells. Menthol (500 µM) induced Ca2+ oscillations in both cell lines, thus independent of TRPM8, which were however dependent on the production of inositol trisphosphate. Results based on pharmacological tools point to an involvement of the purinergic pathway in menthol-evoked Ca2+ responses. Finally, menthol (50–500 µM) decreased cell viability and induced oxidative stress independently of the presence of TRPM8 channels, despite that temperature-evoked TRPM8-mediated inward currents were significantly decreased in TRPM8-knockout Du 145 cells compared to wild type Du 145 cells. © 2017 The Authors}, keywords = {APOPTOSIS; TEMPERATURE; ARTICLE; MEMBRANE DEPOLARIZATION; human; priority journal; controlled study; human cell; protein expression; calcium cell level; reactive oxygen metabolite; Cell viability; Calcium Signaling; purinergic receptor; calcium transport; cancer cell; mitochondrial membrane potential; menthol; Purinergic signaling; inositol trisphosphate; ECTOPIC EXPRESSION; Prostate cancer cell line; transient receptor potential channel M8; Breast cancer cell line; CA2+ OSCILLATIONS; DU145 cell line; TRPM8; Oxidative stress}, year = {2018}, eissn = {2213-2317}, pages = {439-449} } @article{MTMT:3260664, title = {Pellitorine, an extract of Tetradium daniellii, is an antagonist of the ion channel TRPV1}, url = {https://m2.mtmt.hu/api/publication/3260664}, author = {Oláh, Zoltán and Rédei, Dóra and Pecze, László and Vizler, Csaba and Jósvay, Katalin and Forgó, Péter and Winter, Zoltán and Dombi, György and Szakonyi, Gerda and Hohmann, Judit}, doi = {10.1016/j.phymed.2017.06.006}, journal-iso = {PHYTOMEDICINE}, journal = {PHYTOMEDICINE: INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY}, volume = {34}, unique-id = {3260664}, issn = {0944-7113}, year = {2017}, eissn = {1618-095X}, pages = {44-49}, orcid-numbers = {Rédei, Dóra/0000-0002-5013-247X; Forgó, Péter/0000-0002-0279-6896; Szakonyi, Gerda/0000-0002-4366-4283; Hohmann, Judit/0000-0002-2887-6392} } @article{MTMT:3257096, title = {Molecular surgery concept from bench to bedside: A focus on TRPV1+ pain-sensing neurons}, url = {https://m2.mtmt.hu/api/publication/3257096}, author = {Pecze, L and Viskolcz, Béla and Oláh, Zoltán}, doi = {10.3389/fphys.2017.00378}, journal-iso = {FRONT PHYSIOL}, journal = {FRONTIERS IN PHYSIOLOGY}, volume = {8}, unique-id = {3257096}, abstract = {"Molecular neurosurgery" is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell. © 2017 Pecze, Viskolcz and Oláh.}, keywords = {APOPTOSIS; RESINIFERATOXIN; SENSORY NEURONS; NECROSIS; VANILLOIDS; CAPSAICIN; TRPV1}, year = {2017}, eissn = {1664-042X} } @article{MTMT:3250677, title = {Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels}, url = {https://m2.mtmt.hu/api/publication/3250677}, author = {Naziroglu, M and Cig, B and Blum, W and Vizler, Csaba and Buhala, Andrea and Marton, Annamária and Katona, Róbert László and Jósvay, Katalin and Schwaller, B and Oláh, Zoltán and Pecze, László}, doi = {10.1371/journal.pone.0179950}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {12}, unique-id = {3250677}, issn = {1932-6203}, abstract = {There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 mu M) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 mu M) either alone or together with CAPS (10 mu M). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicinevoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 mu M). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required.}, year = {2017}, eissn = {1932-6203} } @article{MTMT:3095574, title = {Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons}, url = {https://m2.mtmt.hu/api/publication/3095574}, author = {Pecze, L and Jósvay, Katalin and Blum, W and Petrovics, G and Vizler, Csaba and Oláh, Zoltán and Schwaller, B}, doi = {10.1016/j.bbamcr.2016.05.007}, journal-iso = {BBA-MOL CELL RES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH}, volume = {1863}, unique-id = {3095574}, issn = {0167-4889}, abstract = {Vanilloids including capsaicin and resiniferatoxin are potent transient receptor potential vanilloid type I (TRPV1) agonists. TRPV1 overstimulation selectively ablates capsaicin-sensitive sensory neurons in animal models in vivo. The cytotoxic mechanisms are based on strong Na+ and Ca2+ influx via TRPV1 channels, which leads to mitochondrial Ca2+ accumulation and necrotic cell swelling. Increased TRPV1 expression levels are also observed in breast and prostate cancer and derived cell lines. Here, we examined whether potent agonist-induced over stimulation mediated by TRPV1 might represent a means for the eradication of prostate carcinoma (PC-3, Du 145, LNCaP) and breast cancer (MCF7, MDA-MB-231, BT-474) cells in vitro. While rat sensory neurons were highly vanilloid-sensitive, normal rat prostate epithelial cells were resistant in vivo. We found TRPV1 to be expressed in all cancer cell lines at mRNA and protein levels, yet protein expression levels were significantly lower compared to sensory neurons. Treatment of all human carcinoma cell lines with capsaicin didn't lead to overstimulation cytotoxicity in vitro. We assume that the low vanilloid-sensitivity of prostate and breast cancer cells is associated with low expression levels of TRPV1, since ectopic TRPV1 expression rendered them susceptible to the cytotoxic effect of vanilloids evidenced by plateau-type Ca2+ signals, mitochondrial Ca2+ accumulation and Na+- and Ca2+-dependent membrane disorganization. Moreover, long-term monitoring revealed that merely the ectopic expression of TRPV1 stopped cell proliferation and often induced apoptotic processes via strong activation of caspase-3 activity. Our results indicate that specific targeting of TRPV1 function remains a putative strategy for cancer treatment. (C) 2016 The Authors. Published by Elsevier B.V.}, keywords = {EXPRESSION; APOPTOSIS; RESINIFERATOXIN; SENSORY NEURONS; CAPSAICIN-RECEPTOR; NERVOUS-SYSTEM; ION-CHANNEL; EPITHELIAL-CELLS; TRPV1; MOLECULAR-MECHANISMS; breast cancer; Prostate cancer; Ca2+ signaling; RECEPTOR POTENTIAL VANILLOID-1}, year = {2016}, eissn = {1879-2596}, pages = {2054-2064} } @article{MTMT:3087152, title = {Competitive inhibition of TRPV1 – calmodulin interaction by vanilloids}, url = {https://m2.mtmt.hu/api/publication/3087152}, author = {Hetényi, Anasztázia and Németh, Lukács and Wéber, Edit and Szakonyi, Gerda and Winter, Zoltán and Jósvay, Katalin and Bartus, Éva and Oláh, Zoltán and Martinek, Tamás}, doi = {10.1002/1873-3468.12267}, journal-iso = {FEBS LETT}, journal = {FEBS LETTERS}, volume = {590}, unique-id = {3087152}, issn = {0014-5793}, abstract = {There is enormous interest toward vanilloid agonists of the pain receptor TRPV1 in analgesic therapy, but the mechanisms of their sensory neuron-blocking effects at high or repeated doses are still a matter of debate. Our results have demonstrated that capsaicin and resiniferatoxin form nanomolar complexes with calmodulin, and competitively inhibit TRPV1-calmodulin interaction. These interactions involve the protein recognition interface of calmodulin, which is responsible for all of the cell-regulatory calmodulin-protein interactions. These results draw attention to a previously unknown vanilloid target, which may contribute to the explanation of the paradoxical pain-modulating behavior of these important pharmacons.}, keywords = {BINDING; ACTIVATION; RESINIFERATOXIN; RESINIFERATOXIN; SENSITIVITY; CAPSAICIN; CAPSAICIN; TRPV1; CALMODULIN; CALMODULIN; Biophysics; Biochemistry & Molecular Biology; TRPV1 CHANNEL; CA2+-DEPENDENT DESENSITIZATION; RECEPTOR TRPV1}, year = {2016}, eissn = {1873-3468}, pages = {2768-2775}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Wéber, Edit/0000-0002-5904-0619; Szakonyi, Gerda/0000-0002-4366-4283; Bartus, Éva/0000-0001-9976-6978; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:2763894, title = {Besides neuro-imaging, the Thy1-YFP mouse could serve for visualizing experimental tumours, inflammation and wound-healing}, url = {https://m2.mtmt.hu/api/publication/2763894}, author = {Jósvay, Katalin and Winter, Zoltán and Katona, Róbert László and Pecze, László and Marton, Annamária and Buhala, Andrea and Szakonyi, Gerda and Oláh, Zoltán and Vizler, Csaba}, doi = {10.1038/srep06776}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {4}, unique-id = {2763894}, issn = {2045-2322}, abstract = {The B6.Cg-Tg(Thy1-YFP)16Jrs/J transgenic mouse strain, widely used to study neuronal development and regeneration, expresses the yellow fluorescent protein (YFP) in the peripheral nerves and the central nervous system under the control of regulatory sequences of the Thy1 gene. The Thy1 (CD90) cell surface glycoprotein is present on many cell types besides neurons, and is known to be involved in cell adhesion, migration and signal transduction. We hypothesized that Thy1-activating conditions could probably activate the truncated Thy1 regulatory sequences used in the Thy1-YFP construct, resulting in YFP transgene expression outside the nervous system. We demonstrated that the stroma of subcutaneous tumours induced by the injection of 4T1 or MC26 carcinoma cells into BALB/c(Thy1-YFP) mice, carrying the same construct, indeed expressed the YFP transgene. In the tumour mass, the yellow-green fluorescent stromal cells were clearly distinguishable from 4T1 carcinoma cells stably transfected with red fluorescent protein. Local inflammation induced by subcutaneous injection of complete Freund's adjuvant, as well as the experimental wound-healing milieu, also triggered YFP fluorescence in both the BALB/c(Thy1-YFP) and B6.Cg-Tg(Thy1-YFP)16Jrs/J mice, pointing to eventual overlapping pathways of wound-healing, inflammation and tumour growth.}, year = {2014}, eissn = {2045-2322}, pages = {6776-6783}, orcid-numbers = {Szakonyi, Gerda/0000-0002-4366-4283} } @article{MTMT:2763893, title = {Propylene-Glycol Aggravates LPS-Induced Sepsis through Production of TNF-alpha and IL-6}, url = {https://m2.mtmt.hu/api/publication/2763893}, author = {Marton, Annamária and Kolozsi, Csongor and Kusz, Erzsébet and Oláh, Zoltán and Letoha, Tamás and Vizler, Csaba and Pecze, László}, journal-iso = {IRAN J IMMUNOL}, journal = {IRANIAN JOURNAL OF IMMUNOLOGY}, volume = {11}, unique-id = {2763893}, issn = {1735-1383}, abstract = {Background: Propylene glycol (1,2-propanediol, PG) is a commonly used solvent for oral, intravenous, as well as topical pharmaceutical preparations. While PG is generally considered to be safe, it has been known that large intravenous doses given over a short period of time can be toxic. Objective: To evaluate the effect of PG in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS). Methods: Balb/c mice were treated with LPS (1 mg/kg b. w., i. p.) with or without PG (5 g/kg b. w. i. v.). The survival rate and the production of inflammatory cytokines were measured. In RAW264.7 mouse macrophages encoding NF-kappa B-luc reporter gene, the nuclear transcription factor kappaB (NF-kappa B) activation was measured. Results: We found that intravenous PG increased the mortality rate in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS) in mice. In accordance with that, PG enhanced LPS-induced production of inflammatory cytokines, including tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) in vivo. PG also increased the LPS-induced macrophage activation in vitro as detected by measuring NF-kappa B activation. Conclusion: Our results indicate that drugs containing high doses of PG can pose a risk when administered to patients suffering from or prone to Gram negative bacterial infection.}, year = {2014}, eissn = {1735-367X}, pages = {113-122} } @article{MTMT:2341377, title = {Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel – an overview of the current mutational data}, url = {https://m2.mtmt.hu/api/publication/2341377}, author = {Winter, Zoltán and Buhala, Andrea and Ötvös, Ferenc and Jósvay, Katalin and Vizler, Csaba and Dombi, György and Szakonyi, Gerda and Oláh, Zoltán}, doi = {10.1186/1744-8069-9-30}, journal-iso = {MOL PAIN}, journal = {MOLECULAR PAIN}, volume = {9}, unique-id = {2341377}, issn = {1744-8069}, year = {2013}, eissn = {1744-8069}, orcid-numbers = {Szakonyi, Gerda/0000-0002-4366-4283} }