TY - JOUR AU - Oláh, Zoltán AU - László, Pecze AU - Éva, Kocsis AU - Viskolcz, Béla TI - A “keto-enol” plaque buster mechanism to diminish Alzheimer’s β-Amyloid burden JF - BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS J2 - BIOCHEM BIOPH RES CO VL - 532 PY - 2020 IS - 1 SP - 82 EP - 87 PG - 6 SN - 0006-291X DO - 10.1016/j.bbrc.2020.07.086 UR - https://m2.mtmt.hu/api/publication/31604811 ID - 31604811 N1 - Export Date: 15 May 2021 CODEN: BBRCA Correspondence Address: László, P.; University of FribourgSwitzerland; email: laszlo.pecze@unifr.ch LA - English DB - MTMT ER - TY - JOUR AU - Nazıroğlu, M AU - Blum, W AU - Jósvay, Katalin AU - Çiğ, B AU - Henzi, T AU - Oláh, Zoltán AU - Vizler, Csaba AU - Schwaller, B AU - Pecze, László TI - Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells JF - REDOX BIOLOGY J2 - REDOX BIOL VL - 14 PY - 2018 SP - 439 EP - 449 PG - 11 SN - 2213-2317 DO - 10.1016/j.redox.2017.10.009 UR - https://m2.mtmt.hu/api/publication/3318960 ID - 3318960 N1 - Cited By :18 Export Date: 16 September 2022 AB - 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 LA - English DB - MTMT ER - TY - JOUR AU - Oláh, Zoltán AU - Rédei, Dóra AU - Pecze, László AU - Vizler, Csaba AU - Jósvay, Katalin AU - Forgó, Péter AU - Winter, Zoltán AU - Dombi, György AU - Szakonyi, Gerda AU - Hohmann, Judit TI - Pellitorine, an extract of Tetradium daniellii, is an antagonist of the ion channel TRPV1 JF - PHYTOMEDICINE: INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY J2 - PHYTOMEDICINE VL - 34 PY - 2017 SP - 44 EP - 49 PG - 6 SN - 0944-7113 DO - 10.1016/j.phymed.2017.06.006 UR - https://m2.mtmt.hu/api/publication/3260664 ID - 3260664 LA - English DB - MTMT ER - TY - JOUR AU - Pecze, L AU - Viskolcz, Béla AU - Oláh, Zoltán TI - Molecular surgery concept from bench to bedside: A focus on TRPV1+ pain-sensing neurons JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 8 PY - 2017 IS - JUN SN - 1664-042X DO - 10.3389/fphys.2017.00378 UR - https://m2.mtmt.hu/api/publication/3257096 ID - 3257096 N1 - Cited By :9 Export Date: 16 September 2022 AB - "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. LA - English DB - MTMT ER - TY - JOUR AU - Naziroglu, M AU - Cig, B AU - Blum, W AU - Vizler, Csaba AU - Buhala, Andrea AU - Marton, Annamária AU - Katona, Róbert László AU - Jósvay, Katalin AU - Schwaller, B AU - Oláh, Zoltán AU - Pecze, László TI - Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels JF - PLOS ONE J2 - PLOS ONE VL - 12 PY - 2017 IS - 6 PG - 19 SN - 1932-6203 DO - 10.1371/journal.pone.0179950 UR - https://m2.mtmt.hu/api/publication/3250677 ID - 3250677 N1 - OA gold AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Pecze, L AU - Jósvay, Katalin AU - Blum, W AU - Petrovics, G AU - Vizler, Csaba AU - Oláh, Zoltán AU - Schwaller, B TI - Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH J2 - BBA-MOL CELL RES VL - 1863 PY - 2016 IS - 8 SP - 2054 EP - 2064 PG - 11 SN - 0167-4889 DO - 10.1016/j.bbamcr.2016.05.007 UR - https://m2.mtmt.hu/api/publication/3095574 ID - 3095574 N1 - Megjegyzés-27115000 N1 Funding details: 130680, SNF, Stavros Niarchos Foundation AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Hetényi, Anasztázia AU - Németh, Lukács AU - Wéber, Edit AU - Szakonyi, Gerda AU - Winter, Zoltán AU - Jósvay, Katalin AU - Bartus, Éva AU - Oláh, Zoltán AU - Martinek, Tamás TI - Competitive inhibition of TRPV1 – calmodulin interaction by vanilloids JF - FEBS LETTERS J2 - FEBS LETT VL - 590 PY - 2016 IS - 16 SP - 2768 EP - 2775 PG - 8 SN - 0014-5793 DO - 10.1002/1873-3468.12267 UR - https://m2.mtmt.hu/api/publication/3087152 ID - 3087152 N1 - Funding Agency and Grant Number: Hungarian Academy of Sciences; Lendulet Program [LP-2011-009]; MTA Postdoctoral Fellowship E.W., Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]; Richter Gedeon Talentum Alapitvany; European Union; State of Hungary; European Social Fund [TAMOP-4.2.4.A/ 2-11/1-2012-0001]\n Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet Program (LP-2011-009), MTA Postdoctoral Fellowship E.W., Gedeon Richter Plc. (TP7-017), the Hungarian Research Foundation (OTKA K112442) and Financial support from Richter Gedeon Talentum Alapitvany (Ph.D. Scholarship to E.B.). This research was supported by the European Union and the State of Hungary, cofinanced by the European Social Fund in the framework of TAMOP-4.2.4.A/ 2-11/1-2012-0001 'National Excellence Program'.\n Funding Agency and Grant Number: Hungarian Academy of Sciences; Lendulet Program [LP-2011-009]; MTA Postdoctoral Fellowship E.W., Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]; Richter Gedeon Talentum Alapitvany; European Union; State of Hungary; European Social Fund [TAMOP-4.2.4.A/ 2-11/1-2012-0001] Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet Program (LP-2011-009), MTA Postdoctoral Fellowship E.W., Gedeon Richter Plc. (TP7-017), the Hungarian Research Foundation (OTKA K112442) and Financial support from Richter Gedeon Talentum Alapitvany (Ph.D. Scholarship to E.B.). This research was supported by the European Union and the State of Hungary, cofinanced by the European Social Fund in the framework of TAMOP-4.2.4.A/ 2-11/1-2012-0001 'National Excellence Program'. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Jósvay, Katalin AU - Winter, Zoltán AU - Katona, Róbert László AU - Pecze, László AU - Marton, Annamária AU - Buhala, Andrea AU - Szakonyi, Gerda AU - Oláh, Zoltán AU - Vizler, Csaba TI - Besides neuro-imaging, the Thy1-YFP mouse could serve for visualizing experimental tumours, inflammation and wound-healing JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 4 PY - 2014 SP - 6776 PG - 7 SN - 2045-2322 DO - 10.1038/srep06776 UR - https://m2.mtmt.hu/api/publication/2763894 ID - 2763894 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Marton, Annamária AU - Kolozsi, Csongor AU - Kusz, Erzsébet AU - Oláh, Zoltán AU - Letoha, Tamás AU - Vizler, Csaba AU - Pecze, László TI - Propylene-Glycol Aggravates LPS-Induced Sepsis through Production of TNF-alpha and IL-6 JF - IRANIAN JOURNAL OF IMMUNOLOGY J2 - IRAN J IMMUNOL VL - 11 PY - 2014 IS - 2 SP - 113 EP - 122 PG - 10 SN - 1735-1383 UR - https://m2.mtmt.hu/api/publication/2763893 ID - 2763893 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Winter, Zoltán AU - Buhala, Andrea AU - Ötvös, Ferenc AU - Jósvay, Katalin AU - Vizler, Csaba AU - Dombi, György AU - Szakonyi, Gerda AU - Oláh, Zoltán TI - Functionally important amino acid residues in the transient receptor potential vanilloid 1 (TRPV1) ion channel – an overview of the current mutational data JF - MOLECULAR PAIN J2 - MOL PAIN VL - 9 PY - 2013 IS - 1 PG - 29 SN - 1744-8069 DO - 10.1186/1744-8069-9-30 UR - https://m2.mtmt.hu/api/publication/2341377 ID - 2341377 LA - English DB - MTMT ER -