TY  - JOUR
AU  - Debreczeni, Dorina
AU  - Baukál, D.
AU  - Pergel, Enikő
AU  - Veres, Irén
AU  - Czirják, Gábor
TI  - Critical contribution of the intracellular C-terminal region to TRESK channel activity is revealed by the epithelial Na+ current ratio method
JF  - JOURNAL OF BIOLOGICAL CHEMISTRY
J2  - J BIOL CHEM
VL  - 299
PY  - 2023
IS  - 6
PG  - 17
SN  - 0021-9258
DO  - 10.1016/j.jbc.2023.104737
UR  - https://m2.mtmt.hu/api/publication/33917496
ID  - 33917496
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Kolacsek, Orsolya
AU  - Wachtl, Gerda Gabriella
AU  - Fóthi, Ábel
AU  - Schamberger, Anita
AU  - Sándor, Sára Anna
AU  - Pergel, Enikő
AU  - Varga, Nóra
AU  - Raskó, Tamás
AU  - Izsvák, Zsuzsa
AU  - Apáti, Ágota
AU  - Orbán, Tamás I.
TI  - Functional indications for transposase domestications – Characterization of the human piggyBac transposase derived (PGBD) activities
JF  - GENE
J2  - GENE
VL  - 834
PY  - 2022
PG  - 12
SN  - 0378-1119
DO  - 10.1016/j.gene.2022.146609
UR  - https://m2.mtmt.hu/api/publication/32873583
ID  - 32873583
AB  - Transposable elements are widespread in all living organisms. In addition to self-reproduction, they are a major source of genetic variation that drives genome evolution but our knowledge of the functions of human genes derived from transposases is limited. There are examples of transposon-derived, domesticated human genes that lost (SETMAR) or retained (THAP9) their transposase activity, however, several remnants in the human genome have not been thoroughly investigated yet. These include the five human piggyBac-derived sequences (PGBD1-5) which share ancestry with the Trichoplusia ni originated piggyBac (PB) transposase. Since PB is widely used in gene delivery applications, the potential activities of endogenous PGBDs are important to address. However, previous data is controversial, especially with the claimed transposition activity of PGBD5, it awaits further investigations. Here, we aimed to systematically analyze all five human PGBD proteins from several aspects, including phylogenetic conservation, potential transposase activity, expression pattern and their regulation in different stress conditions. Among PGBDs, PGBD5 is under the highest purifying selection, and exhibits the most cell type specific expression pattern. In a two-component vector system, none of the human PGBDs could mobilize either the insect PB transposon or the endogenous human PB-like MER75 and MER85 elements with intact terminal sequences. When cells were exposed to various stress conditions, including hypoxia, oxidative or UV stress, the expression profiles of all PGBDs showed different, often cell type specific responses; however, the pattern of PGBD5 in most cases had the opposite tendency than that of the other piggyBac-derived elements. Taken together, our results indicate that human PGBD elements did not retain their mobilizing activity, but their cell type specific, and cellular stress related expression profiles point toward distinct domesticated functions that require further characterization.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Pergel, Enikő
AU  - Veres, Irén
AU  - Csigi, G.I.
AU  - Czirják, Gábor
TI  - Translocation of TMEM175 lysosomal potassium channel to the plasma membrane by dynasore compounds
JF  - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
J2  - INT J MOL SCI
VL  - 22
PY  - 2021
IS  - 19
PG  - 30
SN  - 1661-6596
DO  - 10.3390/ijms221910515
UR  - https://m2.mtmt.hu/api/publication/32369259
ID  - 32369259
LA  - English
DB  - MTMT
ER  - 

TY  - THES
AU  - Pergel, Enikő
TI  - A TRESK háttér K+ csatorna protein kináz C általi szabályozásának vizsgálata
PY  - 2020
DO  - 10.14753/SE.2020.2362
UR  - https://m2.mtmt.hu/api/publication/31921498
ID  - 31921498
LA  - Hungarian
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Pergel, Enikő
AU  - Lengyel, Miklós
AU  - Enyedi, Péter
AU  - Czirják, Gábor
TI  - TRESK (K2P18.1) Background Potassium Channel is Activated by Novel-Type Protein Kinase C via Dephosphorylation
JF  - MOLECULAR PHARMACOLOGY
J2  - MOL PHARMACOL
VL  - 95
PY  - 2019
IS  - 6
SP  - 661
EP  - 672
PG  - 8
SN  - 0026-895X
DO  - 10.1124/mol.119.116269
UR  - https://m2.mtmt.hu/api/publication/30654930
ID  - 30654930
AB  - TRESK (K2P18.1) background K+ channel is a major determinant of the excitability of primary sensory neurons. It has been reported that human TRESK is activated by the protein kinase C (PKC) activator PMA (phorbol 12-myristate 13-acetate) in Xenopus oocytes. In the present study, we investigated the mechanism of this PKC-dependent TRESK regulation. We show that TRESK is activated by the coexpression of the novel-type PKC isoforms eta and epsilon. The effect of PKC is not mediated by calcineurin phosphatase, which is known to evoke the calcium-dependent TRESK activation. The mutations of the calcineurin-binding sites in the channel (PQAAAS-AQAP) did not influence the PMA-induced increase of potassium current. In sharp contrast, the mutations of the target residue of calcineurin in TRESK, S264A and S264E, prevented the effect of PMA. The enforced phosphorylation of S264 by the coexpression of a microtubule-affinity regulating kinase construct (MARK2Δ) also abolished the PKC-dependent TRESK activation. These results suggest that in addition to calcineurin, PKC also regulates TRESK by changing the phosphorylation status of S264. The coexpression of PKC slowed down the recovery of the K+ current to the resting state after the calcineurin-dependent dephosphorylation of TRESK. Therefore, the likely mechanism of action is the PKC-dependent inhibition of the kinase responsible for the (re)phosphorylation of the channel at S264. The PKC-dependent dephosphorylation of TRESK protein was also detected by the Phos-tag SDS-PAGE method. In summary, the activation of novel-type PKC results in the slow (indirect) dephosphorylation of TRESK at the regulatory residue S264 in a calcineurin-independent manner.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Lengyel, Miklós
AU  - Erdélyi, Ferenc
AU  - Pergel, Enikő
AU  - Polonkáné Bálint, Ágnes
AU  - Dobolyi, Alice
AU  - Bozsaki, Peter
AU  - Dux, Mária
AU  - Király, Kornél P
AU  - Hegedűs, Tamás
AU  - Czirják, Gábor
AU  - Mátyus, Péter
AU  - Enyedi, Péter
TI  - Chemically Modified Derivatives of the Activator Compound Cloxyquin Exert Inhibitory Effect on TRESK (K2P18.1) Background Potassium Channel
JF  - MOLECULAR PHARMACOLOGY
J2  - MOL PHARMACOL
VL  - 95
PY  - 2019
IS  - 6
SP  - 652
EP  - 660
PG  - 9
SN  - 0026-895X
DO  - 10.1124/mol.118.115626
UR  - https://m2.mtmt.hu/api/publication/30654928
ID  - 30654928
AB  - Cloxyquin has been reported as a specific activator of TRESK (K2P18.1, TWIK-related spinal cord K+ channel) background potassium channel. In this study, we have synthetized chemically modified analogues of cloxyquin and tested their effects on TRESK and other K2P channels. The currents of murine K2P channels, expressed heterologously in Xenopus oocytes, were measured by two-electrode voltage clamp, whereas the native background K+ conductance of mouse dorsal root ganglion (DRG) neurons was examined by the whole-cell patch clamp method. Some of the analogues retained the activator character of the parent compound, but more interestingly, other derivatives inhibited mouse TRESK current. The inhibitor analogues (A2764 and A2793) exerted state-dependent effect. The degree of inhibition by 100 µM A2764 (77.8±1.5%, n=6) was larger in the activated state of TRESK (i.e. after calcineurin-dependent stimulation) than in the resting state of the channel (42.8±4.3% inhibition, n=7). The selectivity of the inhibitor compounds was tested on several K2P channels. A2793 inhibited TASK-1 (100 µM, 53.4±6%, n=5), while A2764 was more selective for TRESK, it only moderately influenced TREK-1 and TALK-1. The effect of A2764 was also examined on the background K+ currents of DRG neurons. A subpopulation of DRG neurons, prepared from wild-type animals, expressed background K+ currents sensitive to A2764, while the inhibitor did not affect the currents in the DRG neurons of TRESK-deficient mice. Accordingly, A2764 may prove to be useful for the identification of TRESK current in native cells, and for the investigation of the role of the channel in nociception and migraine.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Kubinyi, Enikő
AU  - Bence, Melinda
AU  - Koller, D
AU  - Wan, M
AU  - Pergel, Enikő
AU  - Rónai, Zsolt
AU  - Sasvári-Székely, Mária
AU  - Miklósi, Ádám
TI  - Oxytocin and Opioid Receptor Gene Polymorphisms Associated with Greeting Behavior in Dogs
JF  - FRONTIERS IN PSYCHOLOGY
J2  - FRONT PSYCHOL
VL  - 8
PY  - 2017
PG  - 8
SN  - 1664-1078
DO  - 10.3389/fpsyg.2017.01520
UR  - https://m2.mtmt.hu/api/publication/3291101
ID  - 3291101
N1  - Funding Agency and Grant Number: European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programmeEuropean Research Council (ERC) [680040]; Hungarian Academy of SciencesHungarian Academy of Sciences [MTA 01 031]; Janos Bolyai Research ScholarshipHungarian Academy of Sciences; Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [K100695, ANN107726]; WWTF [CS11-026]
            Funding text: We thank Borbala Turcsan and Lisa Wallis for useful comments on a previous version of the manuscript. We are grateful for Judit Banffyne Vas, Ildiko Bruder, Anita Illes, Borbala Turcsan, and Anna Vargane Kis, who helped in the behavioral testing of the dogs. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 680040), the Hungarian Academy of Sciences (MTA 01 031) and the Janos Bolyai Research Scholarship (for EK), the Hungarian Scientific Research Fund (K100695; ANN107726), and the WWTF (CS11-026).
AB  - Meeting humans is an everyday experience for most companion dogs, and their behavior in these situations and its genetic background is of major interest. Previous research in our laboratory reported that in German shepherd dogs the lack of G allele, and in Border collies the lack of A allele, of the oxytocin receptor gene (OXTR) 19208A/G single nucleotide polymorphism (SNP) was linked to increased friendliness, which suggests that although broad traits are affected by genetic variability, the specific links between alleles and behavioral variables might be breed-specific. In the current study, we found that Siberian huskies with the A allele approached a friendly unfamiliar woman less frequently in a greeting test, which indicates that certain polymorphisms are related to human directed behavior, but that the relationship patterns between polymorphisms and behavioral phenotypes differ between populations. This finding was further supported by our next investigation. According to primate studies, endogenous opioid peptide (e.g., endorphins) receptor genes have also been implicated in social relationships. Therefore, we examined the rs21912990 of the OPRM1 gene. Firstly, we found that the allele frequencies of Siberian huskies and gray wolves were similar, but differed from that of Border collies and German shepherd dogs, which might reflect their genetic relationship. Secondly, we detected significant associations between the OPRM1 SNP and greeting behavior among German shepherd dogs and a trend in Border collies, but we could not detect an association in Siberian huskies. Although our results with OXTR and OPRM1 gene variants should be regarded as preliminary due to the relatively low sample size, they suggest that (1) OXTR and OPRM1 gene variants in dogs affect human-directed social behavior and (2) their effects differ between breeds.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Kolacsek, Orsolya
AU  - Pergel, Enikő
AU  - Varga, Nóra
AU  - Apáti, Ágota
AU  - Orbán, Tamás I.
TI  - Ct shift: A novel and accurate real-time PCR quantification model for direct comparison of different nucleic acid sequences and its application for transposon quantifications
JF  - GENE
J2  - GENE
VL  - 598
PY  - 2017
SP  - 43
EP  - 49
PG  - 7
SN  - 0378-1119
DO  - 10.1016/j.gene.2016.10.035
UR  - https://m2.mtmt.hu/api/publication/3148390
ID  - 3148390
AB  - There are numerous applications of quantitative PCR for both diagnostic and basic research. As in many other techniques the basis of quantification is that comparisons are made between different (unknown and known or reference) specimens of the same entity. When the aim is to compare real quantities of different species in samples, one cannot escape their separate precise absolute quantification. We have established a simple and reliable method for this purpose (Ct shift method) which combines the absolute and the relative approach. It requires a plasmid standard containing both sequences of amplicons to be compared (e.g. the target of interest and the endogenous control). It can serve as a reference sample with equal copies of templates for both targets. Using the DeltaDeltaCt formula we can quantify the exact ratio of the two templates in each unknown sample. The Ct shift method has been successfully applied for transposon gene copy measurements, as well as for comparison of different mRNAs in cDNA samples. This study provides the proof of concept and introduces some potential applications of the method; the absolute nature of results even without the need for real reference samples can contribute to the universality of the method and comparability of different studies.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szebényi, Kornélia
AU  - Füredi, András
AU  - Kolacsek, Orsolya
AU  - Pergel, Enikő
AU  - Bősze, Zsuzsanna
AU  - Bender, B
AU  - Vajdovich, Péter
AU  - Tóvári, József
AU  - Homolya, László
AU  - Szakács, Gergely
AU  - Héja, László
AU  - Enyedi, Ágnes
AU  - Sarkadi, Balázs
AU  - Apáti, Ágota
AU  - Orbán, Tamás I.
TI  - Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling
JF  - SCIENTIFIC REPORTS
J2  - SCI REP
VL  - 5
PY  - 2015
PG  - 14
SN  - 2045-2322
DO  - 10.1038/srep12645
UR  - https://m2.mtmt.hu/api/publication/2938283
ID  - 2938283
AB  - In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver and blood cells. No pathological alterations were found in these animals and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects and provide evidence for the role of Na+/Ca2+ exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Vargáné Kis, Anna
AU  - Bence, Melinda
AU  - Lakatos, Gabriella
AU  - Pergel, Enikő
AU  - Turcsán, Borbála
AU  - Pluijmakers, J
AU  - Vas, J
AU  - Molnár, Zsuzsanna
AU  - Brúder, I
AU  - Földi, L
AU  - Sasvári-Székely, Mária
AU  - Miklósi, Ádám
AU  - Rónai, Zsolt
AU  - Kubinyi, Enikő
TI  - Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris)
JF  - PLOS ONE
J2  - PLOS ONE
VL  - 9
PY  - 2014
IS  - 1
PG  - 9
SN  - 1932-6203
DO  - 10.1371/journal.pone.0083993
UR  - https://m2.mtmt.hu/api/publication/2500104
ID  - 2500104
N1  - Megjegyzés-26874084
N1 Molecular Sequence Numbers: GENBANK: NC_006602;
AB  - The oxytocin system has a crucial role in human sociality; 
several results prove that polymorphisms of the oxytocin 
receptor gene are related to complex social behaviors in humans. 
Dogs' parallel evolution with humans and their adaptation to the 
human environment has made them a useful species to model human 
social interactions. Previous research indicates that dogs are 
eligible models for behavioral genetic research, as well. Based 
on these previous findings, our research investigated 
associations between human directed social behaviors and two 
newly described (−212AG, 19131AG) and one known (rs8679684) 
single nucleotide polymorphisms (SNPs) in the regulatory regions 
(5′ and 3′ UTR) of the oxytocin receptor gene in German Shepherd 
(N = 104) and Border Collie (N = 103) dogs. Dogs' behavior 
traits have been estimated in a newly developed test series 
consisting of five episodes: Greeting by a stranger, Separation 
from the owner, Problem solving, Threatening approach, Hiding of 
the owner. Buccal samples were collected and DNA was isolated 
using standard protocols. SNPs in the 3′ and 5′ UTR regions were 
analyzed by polymerase chain reaction based techniques followed 
by subsequent electrophoresis analysis. The gene–behavior 
association analysis suggests that oxytocin receptor gene 
polymorphisms have an impact in both breeds on (i) proximity 
seeking towards an unfamiliar person, as well as their owner, 
and on (ii) how friendly dogs behave towards strangers, although 
the mediating molecular regulatory mechanisms are yet unknown. 
Based on these results, we conclude that similarly to humans, 
the social behavior of dogs towards humans is influenced by the 
oxytocin system.
LA  - English
DB  - MTMT
ER  -