@article{MTMT:32106321,
	title = {The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology},
	url = {https://m2.mtmt.hu/api/publication/32106321},
	author = {Hudak, Anett and Jósvay, Katalin and Racskóné Domonkos, Ildikó and Letoha, Annamária and Szilák, László and Letoha, Tamás},
	doi = {10.3390/ijms22137070},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {32106321},
	issn = {1661-6596},
	abstract = {Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer's disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (A beta). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in A beta pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE-heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated A beta uptake and aggregation. ApoE2 increased the cellular internalization of monomeric A beta, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once A beta aggregated: while ApoE2 reduced the uptake of A beta aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4 ' s tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of A beta pathology.},
	keywords = {BINDING; ALZHEIMERS-DISEASE; IN-VITRO; ENDOCYTOSIS; SURFACE; Syndecans; protein aggregation; APOE; Biochemistry & Molecular Biology; amyloid beta; SH-SY5Y CELLS; HEPARAN-SULFATE PROTEOGLYCANS; GLAND EPITHELIAL-CELLS; APOLIPOPROTEIN-E ISOFORMS; 6-O-SULFATION},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Letoha, Tamás/0000-0002-6035-4009}
}

@article{MTMT:31181444,
	title = {Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage.},
	url = {https://m2.mtmt.hu/api/publication/31181444},
	author = {Barna, Lilla and Walter, Fruzsina and Harazin, András and Bocsik, Alexandra and Kincses, András and Tubak, Vilmos and Jósvay, Katalin and Zvara, Ágnes and Campos-Bedolla, Patricia and Deli, Mária Anna},
	doi = {10.1186/s12987-019-0166-1},
	journal-iso = {FLUIDS BARRIERS CNS},
	journal = {FLUIDS AND BARRIERS OF THE CNS},
	volume = {17},
	unique-id = {31181444},
	issn = {2045-8118},
	abstract = {Excitotoxicity is a central pathological pathway in many neurological diseases with blood-brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces epilepsy and BBB damage in animal models, but the direct effect of kainate on brain endothelial cells has not been studied in detail. Our aim was to examine the direct effects of kainate on cultured cells of the BBB and to test three anti-inflammatory and antioxidant drugs used in clinical practice, simvastatin, edaravone and dexamethasone, to protect against kainate-induced changes.Primary rat brain endothelial cell, pericyte and astroglia cultures were used to study cell viability by impedance measurement. BBB permeability was measured on a model made from the co-culture of the three cell types. The production of nitrogen monoxide and reactive oxygen species was followed by fluorescent probes. The mRNA expression of kainate receptors and nitric oxide synthases were studied by PCR.Kainate damaged brain endothelial cells and made the immunostaining of junctional proteins claudin-5 and zonula occludens-1 discontinuous at the cell border indicating the opening of the barrier. The permeability of the BBB model for marker molecules fluorescein and albumin and the production of nitric oxide in brain endothelial cells were increased by kainate. Simvastatin, edaravone and dexamethasone protected against the reduced cell viability, increased permeability and the morphological changes in cellular junctions caused by kainate. Dexamethasone attenuated the elevated nitric oxide production and decreased the inducible nitric oxide synthase (NOS2/iNOS) mRNA expression increased by kainate treatment.Kainate directly damaged cultured brain endothelial cells. Simvastatin, edaravone and dexamethasone protected the BBB model against kainate-induced changes. Our results confirmed the potential clinical usefulness of these drugs to attenuate BBB damage.},
	keywords = {DEXAMETHASONE; Permeability; Blood-Brain Barrier; Reactive oxygen species; nitric oxide synthase; SIMVASTATIN; kainate; Edaravone; Brain endothelial cells},
	year = {2020},
	eissn = {2045-8118},
	orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Harazin, András/0000-0002-0904-5606; Tubak, Vilmos/0000-0002-6141-3920; Deli, Mária Anna/0000-0001-6084-6524}
}

@article{MTMT:30935380,
	title = {Contribution of syndecans to cellular uptake and fibrillation of alpha-synuclein and tau},
	url = {https://m2.mtmt.hu/api/publication/30935380},
	author = {Hudak, Anett and Kusz, Erzsebet and Racskóné Domonkos, Ildikó and Jósvay, Katalin and Kodamullil, Alpha Tom and Szilák, László and Hofmann-Apitius, Martin and Letoha, Tamás},
	doi = {10.1038/s41598-019-53038-z},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {9},
	unique-id = {30935380},
	issn = {2045-2322},
	abstract = {Scientific evidence suggests that alpha-synuclein and tau have prion-like properties and that prionlike spreading and seeding of misfolded protein aggregates constitutes a central mechanism for neurodegeneration. Heparan sulfate proteoglycans (HSPGs) in the plasma membrane support this process by attaching misfolded protein fibrils. Despite of intense studies, contribution of specific HSPGs to seeding and spreading of alpha-synuclein and tau has not been explored yet. Here we report that members of the syndecan family of HSPGs mediate cellular uptake of alpha-synuclein and tau fibrils via a lipid-raft dependent and clathrin-independent endocytic route. Among syndecans, the neuron predominant syndecan-3 exhibits the highest affinity for both alpha-synuclein and tau. Syndecan-mediated internalization of alpha-synuclein and tau depends heavily on conformation as uptake via syndecans start to dominate once fibrils are formed. Overexpression of syndecans, on the other hand, reduces cellular uptake of monomeric alpha-synuclein and tau, yet exerts a fibril forming effect on both proteins. Data obtained from syndecan overexpressing cellular models presents syndecans, especially the neuron predominant syndecan-3, as important mediators of seeding and spreading of alpha-synuclein and tau and reveal how syndecans contribute to fundamental molecular events of a-synuclein and tau pathology.},
	year = {2019},
	eissn = {2045-2322}
}

@article{MTMT:30462206,
	title = {Contribution of syndecans to cellular internalization and fibrillation of amyloid-β (1–42)},
	url = {https://m2.mtmt.hu/api/publication/30462206},
	author = {Letoha, Tamás and Hudák, Anett and Kusz, Erzsébet and Pettkó-Szandtner, Aladár and Racskóné Domonkos, Ildikó and Jósvay, Katalin and Hofmann-Apitius, Martin and Szilák, László},
	doi = {10.1038/s41598-018-37476-9},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {9},
	unique-id = {30462206},
	issn = {2045-2322},
	abstract = {Intraneuronal accumulation of amyloid-beta(1-42) (A beta 1-42) is one of the earliest signs of Alzheimer's disease (AD). Cell surface heparan sulfate proteoglycans (HSPGs) have profound influence on the cellular uptake of A beta 1-42 by mediating its attachment and subsequent internalization into the cells. Colocalization of amyloid plaques with members of the syndecan family of HSPGs, along with the increased expression of syndecan-3 and -4 have already been reported in postmortem AD brains. Considering the growing evidence on the involvement of syndecans in the pathogenesis of AD, we analyzed the contribution of syndecans to cellular uptake and fibrillation of A beta 1-42. Among syndecans, the neuron specific syndecan-3 isoform increased cellular uptake of A beta 1-42 the most. Kinetics of A beta 1-42 uptake also proved to be fairly different among SDC family members: syndecan-3 increased A beta 1-42 uptake from the earliest time points, while other syndecans facilitated A beta 1-42 internalization at a slower pace. Internalized A beta 1-42 colocalized with syndecans and flotillins, highlighting the role of lipid-rafts in syndecan-mediated uptake. Syndecan-3 and 4 also triggered fibrillation of A beta 1-42, further emphasizing the pathophysiological relevance of syndecans in plaque formation. Overall our data highlight syndecans, especially the neuron-specific syndecan-3 isoform, as important players in amyloid pathology and show that syndecans, regardless of cell type, facilitate key molecular events in neurodegeneration.},
	year = {2019},
	eissn = {2045-2322}
}

@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: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:2990307,
	title = {Involvement of small heat shock proteins, trehalose, and lipids in the thermal stress management in Schizosaccharomyces pombe.},
	url = {https://m2.mtmt.hu/api/publication/2990307},
	author = {Glatz, Attila and Pilbat, Ana Maria and Nemeth, GL and Kontár, Katalin and Jósvay, Katalin and Hunya, Ákos and Udvardy, Andor and Gombos, Imre and Péter, Mária and Balogh, Gábor and Horváth, Ibolya and Vigh, László and Török, Zsolt},
	doi = {10.1007/s12192-015-0662-4},
	journal-iso = {CELL STRESS CHAPERON},
	journal = {CELL STRESS & CHAPERONES},
	volume = {21},
	unique-id = {2990307},
	issn = {1355-8145},
	abstract = {Changes in the levels of three structurally and functionally different important thermoprotectant molecules, namely small heat shock proteins (sHsps), trehalose, and lipids, have been investigated upon heat shock in Schizosaccharomyces pombe. Both alpha-crystallin-type sHsps (Hsp15.8 and Hsp16) were induced after prolonged high-temperature treatment but with different kinetic profiles. The shsp null mutants display a weak, but significant, heat sensitivity indicating their importance in the thermal stress management. The heat induction of sHsps is different in wild type and in highly heat-sensitive trehalose-deficient (tps1Delta) cells; however, trehalose level did not show significant alteration in shsp mutants. The altered timing of trehalose accumulation and induction of sHsps suggest that the disaccharide might provide protection at the early stage of the heat stress while elevated amount of sHsps are required at the later phase. The cellular lipid compositions of two different temperature-adapted wild-type S. pombe cells are also altered according to the rule of homeoviscous adaptation, indicating their crucial role in adapting to the environmental temperature changes. Both Hsp15.8 and Hsp16 are able to bind to different lipids isolated from S. pombe, whose interaction might provide a powerful protection against heat-induced damages of the membranes. Our data suggest that all the three investigated thermoprotectant macromolecules play a pivotal role during the thermal stress management in the fission yeast.},
	year = {2016},
	eissn = {1466-1268},
	pages = {327-338},
	orcid-numbers = {Hunya, Ákos/0000-0002-4547-9284}
}