@article{MTMT:34790193,
	title = {Lectin-Based Immunophenotyping and Whole Proteomic Profiling of CT-26 Colon Carcinoma Murine Model.},
	url = {https://m2.mtmt.hu/api/publication/34790193},
	author = {Faragó, Anna and Zvara, Ágnes and Tiszlavicz, László and Hunyadi-Gulyás Éva, Csilla and Darula, Zsuzsanna and Hegedűs, Zoltán and Szabó, Enikő and Surguta, Sára Eszter and Tóvári, József and Puskás, László and Szebeni, Gábor},
	doi = {10.3390/ijms25074022},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34790193},
	issn = {1661-6596},
	abstract = {A murine colorectal carcinoma (CRC) model was established. CT26 colon carcinoma cells were injected into BALB/c mice's spleen to study the primary tumor and the mechanisms of cell spread of colon cancer to the liver. The CRC was verified by the immunohistochemistry of Pan Cytokeratin and Vimentin expression. Immunophenotyping of leukocytes isolated from CRC-bearing BALB/c mice or healthy controls, such as CD19+ B cells, CD11+ myeloid cells, and CD3+ T cells, was carried out using fluorochrome-labeled lectins. The binding of six lectins to white blood cells, such as galectin-1 (Gal1), siglec-1 (Sig1), Sambucus nigra lectin (SNA), Aleuria aurantia lectin (AAL), Phytolacca americana lectin (PWM), and galectin-3 (Gal3), was assayed. Flow cytometric analysis of the splenocytes revealed the increased binding of SNA, and AAL to CD3 + T cells and CD11b myeloid cells; and increased siglec-1 and AAL binding to CD19 B cells of the tumor-bearing mice. The whole proteomic analysis of the established CRC-bearing liver and spleen versus healthy tissues identified differentially expressed proteins, characteristic of the primary or secondary CRC tissues. KEGG Gene Ontology bioinformatic analysis delineated the established murine CRC characteristic protein interaction networks, biological pathways, and cellular processes involved in CRC. Galectin-1 and S100A4 were identified as upregulated proteins in the primary and secondary CT26 tumor tissues, and these were previously reported to contribute to the poor prognosis of CRC patients. Modelling the development of liver colonization of CRC by the injection of CT26 cells into the spleen may facilitate the understanding of carcinogenesis in human CRC and contribute to the development of novel therapeutic strategies.},
	keywords = {colorectal carcinoma; lectin binding sugar code; proteomic analysis of murine CRC},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Tóvári, József/0000-0002-5543-3204; Szebeni, Gábor/0000-0002-6998-5632}
}

@article{MTMT:34721386,
	title = {The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma},
	url = {https://m2.mtmt.hu/api/publication/34721386},
	author = {Schaubmayr, W. and Hochreiter, B. and Hunyadi-Gulyás Éva, Csilla and Riegler, L. and Schmidt, K. and Tiboldi, A. and Moser, B. and Klein, K.U. and Krenn, K. and Scharbert, G. and Mohr, T. and Schmid, J.A. and Spittler, A. and Tretter, V.},
	doi = {10.3390/ijms25042415},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34721386},
	issn = {1661-6596},
	abstract = {The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia. © 2024 by the authors.},
	keywords = {ANGIOTENSIN-CONVERTING ENZYME; OXYGEN; TISSUE FACTOR; Extracellular vesicles; Pulmonary endothelium; vesicle proteomics},
	year = {2024},
	eissn = {1422-0067}
}

@article{MTMT:34497633,
	title = {Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats},
	url = {https://m2.mtmt.hu/api/publication/34497633},
	author = {Tukacs, Vanda and Mittli, Dániel Árpád and Hunyadi-Gulyás Éva, Csilla and Darula, Zsuzsanna and Juhász, Gábor Dénes and Kardos, József and Kékesi, Adrienna Katalin},
	doi = {10.1186/s12987-024-00508-w},
	journal-iso = {FLUIDS BARRIERS CNS},
	journal = {FLUIDS AND BARRIERS OF THE CNS},
	volume = {21},
	unique-id = {34497633},
	issn = {2045-8118},
	abstract = {Background: The brain extracellular fluid (ECF), composed of secreted neurotransmitters, metabolites, peptides, and proteins, may reflect brain processes. Analysis of brain ECF may provide new potential markers for synaptic activity or brain damage and reveal additional information on pathological alterations. Epileptic seizure induction is an acute and harsh intervention in brain functions, and it can activate extra- and intracellular proteases, which implies an altered brain secretome. Thus, we applied a 4-aminopyridine (4-AP) epilepsy model to study the hippocampal ECF peptidome alterations upon treatment in rats. Methods: We performed in vivo microdialysis in the hippocampus for 3–3 h of control and 4-AP treatment phase in parallel with electrophysiology measurement. Then, we analyzed the microdialysate peptidome of control and treated samples from the same subject by liquid chromatography-coupled tandem mass spectrometry. We analyzed electrophysiological and peptidomic alterations upon epileptic seizure induction by two-tailed, paired t-test. Results: We detected 2540 peptides in microdialysate samples by mass spectrometry analysis; and 866 peptides—derived from 229 proteins—were found in more than half of the samples. In addition, the abundance of 322 peptides significantly altered upon epileptic seizure induction. Several proteins of significantly altered peptides are neuropeptides (Chgb) or have synapse- or brain-related functions such as the regulation of synaptic vesicle cycle (Atp6v1a, Napa), astrocyte morphology (Vim), and glutamate homeostasis (Slc3a2). Conclusions: We have detected several consequences of epileptic seizures at the peptidomic level, as altered peptide abundances of proteins that regulate epilepsy-related cellular processes. Thus, our results indicate that analyzing brain ECF by in vivo microdialysis and omics techniques is useful for monitoring brain processes, and it can be an alternative method in the discovery and analysis of CNS disease markers besides peripheral fluid analysis. © 2024, The Author(s).},
	keywords = {Animals; Male; PEPTIDES; metabolism; PEPTIDE; SEIZURES; comparative study; amino acid sequence; Extracellular Space; nonhuman; animal model; animal experiment; pathology; slow brain wave; Electroencephalogram; urethan; glial fibrillary acidic protein; area under the curve; in vivo study; seizure; AMIDES; AMIDE; upregulation; brain function; neuropeptide Y; ASTROCYTE; tandem mass spectrometry; Temporal lobe epilepsy; Urethane; MICRODIALYSIS; synapse vesicle; FAMPRIDINE; peptidomics; Gene set enrichment analysis; rat; secretoneurin; Chromogranin B},
	year = {2024},
	eissn = {2045-8118},
	orcid-numbers = {Juhász, Gábor Dénes/0000-0002-0849-6931; Kardos, József/0000-0002-2135-2932; Kékesi, Adrienna Katalin/0000-0003-3042-4878}
}

@article{MTMT:34393301,
	title = {Revisiting the hydrolysis of ampicillin catalyzed by Temoneira-1 β-lactamase, and the effect of Ni(II), Cd(II) and Hg(II)},
	url = {https://m2.mtmt.hu/api/publication/34393301},
	author = {Nafaee, Zeyad Hasan Abdullah and Egyed, Viktória and Jancsó, Attila and Tóth, Annamária and Gerami, Adeleh Mokhles and Dang, Thanh Thien and Heiniger-Schell, Juliana and Hemmingsen, Lars and Hunyadi-Gulyás Éva, Csilla and Peintler, Gábor and Gyurcsik, Béla},
	doi = {10.1002/pro.4809},
	journal-iso = {PROTEIN SCI},
	journal = {PROTEIN SCIENCE},
	volume = {32},
	unique-id = {34393301},
	issn = {0961-8368},
	abstract = {Abstract ?-Lactamases grant resistance to bacteria against ?-lactam antibiotics. The active center of TEM-1 ?-lactamase accommodates a Ser-Xaa-Xaa-Lys motif. TEM-1 ?-lactamase is not a metalloenzyme but it possesses several putative metal ion binding sites. The sites composed of His residue pairs chelate borderline transition metal ions such as Ni(II). In addition, there are many sulfur-containing donor groups that can coordinate soft metal ions such as Hg(II). Cd(II) may bind to both types of the above listed donor groups. No significant change was observed in the circular dichroism spectra of TEM-1 ?-lactamase on increasing the metal ion content of the samples, with the exception of Hg(II) inducing a small change in the secondary structure of the protein. A weak nonspecific binding of Hg(II) was proven by mass spectrometry and 119mHg perturbed angular correlation spectroscopy. The hydrolytic process of ampicillin catalyzed by TEM-1 ?-lactamase was described by the kinetic analysis of the set of full catalytic progress curves, where the slow, yet observable conversion of the primary reaction product into a second one, identified as ampilloic acid by mass spectrometry, needed also to be considered in the applied model. Ni(II) and Cd(II) slightly promoted the catalytic activity of the enzyme while Hg(II) exerted a noticeable inhibitory effect. Hg(II) and Ni(II), applied at 10??M concentration, inhibited the growth of E. coli BL21(DE3) in M9 minimal medium in the absence of ampicillin, but addition of the antibiotic could neutralize this toxic effect by complexing the metal ions.},
	keywords = {Mass spectrometry; Circular Dichroism; Reaction kinetics; 199mHg perturbed angular correlation spectroscopy of γ-rays; TEM-1 β-lactamase; toxic metal binding},
	year = {2023},
	eissn = {1469-896X},
	orcid-numbers = {Jancsó, Attila/0000-0003-2362-0758; Peintler, Gábor/0000-0001-5171-5346; Gyurcsik, Béla/0000-0003-1894-7414}
}

@article{MTMT:34334193,
	title = {Biofilm formation initiating rotifer-specific biopolymer and its predicted components},
	url = {https://m2.mtmt.hu/api/publication/34334193},
	author = {Datki, Zsolt László and Darula, Zsuzsanna and Vedelek, Viktor and Hunyadi-Gulyás Éva, Csilla and Dingmann, Brian J. and Vedelek, Balázs and Kalman, Janos and Urban, Peter and Gyenesei, Attila and Galik-Olah, Zita and Gálik, Bence and Sinka, Rita},
	doi = {10.1016/j.ijbiomac.2023.127157},
	journal-iso = {INT J BIOL MACROMOL},
	journal = {INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES},
	volume = {253},
	unique-id = {34334193},
	issn = {0141-8130},
	abstract = {The rotifer-specific biopolymer, namely Rotimer, is a recently discovered group of the biomolecule family. Rotimer has an active role in the biofilm formation initiated by rotifers (e.g., Euchlanis dilatata or Adineta vaga) or in the female-male sexual interaction of monogononts. To understand the Ca2+- and polarity-dependent formation of this multifunctional viscoelastic material, it is essential to explore its molecular composition. The investigation of the rotifer-enhanced biofilm and Rotimer-inductor conglomerate (RIC) formation yielded several protein candidates to predict the Rotimer-specific main components. The exudate of E. dilatata males was primarily applied from different biopolimer-containing samples (biofilm or RIC). The advantage of males over females lies in their degenerated digestive system and simple anatomy. Thus, their exudate is less contaminated with food and endosymbiont elements. The sequenced and annotated genome and transcriptome of this species opened the way for identifying Rotimer proteins by mass spectrometry. The predicted rotifer-biopolymer forming components are SCO-spondins and 14-3-3 protein. The characteristics of Rotimer are similar to Reissner's fiber, which is found in the central nervous system of vertebrates and is mainly formed from SCO-spondins. This molecular information serves as a starting point for its interdisciplinary investigation and application in biotechnology, biomedicine, or neurodegeneration-related drug development.},
	keywords = {IN-VIVO; PROTEINS; 14-3-3 PROTEIN; ANTIBODY; Biofilm; Ecotoxicology; Clearance; Chemistry, Applied; Biochemistry & Molecular Biology; Rotimer; SCO-spondin},
	year = {2023},
	eissn = {1879-0003},
	orcid-numbers = {Datki, Zsolt László/0000-0002-2537-4741; Vedelek, Balázs/0000-0001-6981-0026; Sinka, Rita/0000-0003-4040-4184}
}

@article{MTMT:34154576,
	title = {Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects},
	url = {https://m2.mtmt.hu/api/publication/34154576},
	author = {Tornyi, Ilona and Lazar, Jozsef and Pettkó-Szandtner, Aladár and Hunyadi-Gulyás Éva, Csilla and Takács, László Kristóf},
	doi = {10.3390/ijms241814359},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34154576},
	issn = {1661-6596},
	abstract = {The human proteome is more complex than the genetic code predicts it to be. Epitomics, or protein epitome profiling, is a tool for understanding sub-protein level variation. With the ultimate goal to explore C9 proteoforms and their relevance to lung cancer, here we report plasma C9 epitope-associated molecular heterogeneity in plasma samples of lung cancer patients and control subjects. We show three C9 epitopes (BSI0449, BSI0581, BSI0639) with markedly different association with lung cancer (“unaltered”, “upregulated” and “downregulated”). In order to exclude confounding effects, we show first that the three epitope-defining mAbs recognize C9 in purified form and in the natural context, in the human plasma. Then, we present data demonstrating the lack of major epitope interdependence or overlap. The next experiments represent a quest toward the understanding of the molecular basis of apparent disparate association with lung cancer. Using immunochemistry, SDS PAGE and LC-MS/MS technologies, we demonstrate that epitope-specific immunoprecipitates of plasma C9 seem identical regarding peptide sequence. However, we found epitope-specific posttranslational modification and coprecipitated protein composition differences with respect to control and lung cancer plasma. Epitope profiling enabled the classification of hypothetical C9 proteoforms through differential association with lung cancer.},
	year = {2023},
	eissn = {1422-0067}
}

@article{MTMT:34071578,
	title = {Hydrolytic Mechanism of a Metalloenzyme Is Modified by the Nature of the Coordinated Metal Ion},
	url = {https://m2.mtmt.hu/api/publication/34071578},
	author = {Nafaee, Zeyad Hasan Abdullah and Hajdu, Bálint and Hunyadi-Gulyás Éva, Csilla and Gyurcsik, Béla},
	doi = {10.3390/molecules28145511},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {28},
	unique-id = {34071578},
	issn = {1420-3049},
	abstract = {The nuclease domain of colicin E7 cleaves double-strand DNA non-specifically. Zn2+ ion was shown to be coordinated by the purified NColE7 as its native metal ion. Here, we study the structural and catalytic aspects of the interaction with Ni2+, Cu2+ and Cd2+ non-endogenous metal ions and the consequences of their competition with Zn2+ ions, using circular dichroism spectroscopy and intact protein mass spectrometry. An R447G mutant exerting decreased activity allowed for the detection of nuclease action against pUC119 plasmid DNA via agarose gel electrophoresis in the presence of comparable metal ion concentrations. It was shown that all of the added metal ions could bind to the apoprotein, resulting in a minor secondary structure change, but drastically shifting the charge distribution of the protein. Zn2+ ions could not be replaced by Ni2+, Cu2+ and Cd2+. The nuclease activity of the Ni2+-bound enzyme was extremely high in comparison with the other metal-bound forms, and could not be inhibited by the excess of Ni2+ ions. At the same time, this activity was significantly decreased in the presence of equivalent Zn2+, independent of the order of addition of each component of the mixture. We concluded that the Ni2+ ions promoted the DNA cleavage of the enzyme through a more efficient mechanism than the native Zn2+ ions, as they directly generate the nucleophilic OH− ion.},
	year = {2023},
	eissn = {1420-3049},
	orcid-numbers = {Hajdu, Bálint/0000-0003-4024-116X; Hunyadi-Gulyás Éva, Csilla/0000-0003-2089-1499; Gyurcsik, Béla/0000-0003-1894-7414}
}

@article{MTMT:33667360,
	title = {Zinc binding of a Cys2His2-type zinc finger protein is enhanced by the interaction with DNA},
	url = {https://m2.mtmt.hu/api/publication/33667360},
	author = {Hajdu, Bálint and Hunyadi-Gulyás Éva, Csilla and Kato, Kohsuke and Kawaguchi, Atsushi and Nagata, Kyosuke and Gyurcsik, Béla},
	doi = {10.1007/s00775-023-01988-1},
	journal-iso = {J BIOL INORG CHEM},
	journal = {JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY},
	volume = {28},
	unique-id = {33667360},
	issn = {0949-8257},
	year = {2023},
	eissn = {1432-1327},
	pages = {301-315},
	orcid-numbers = {Hajdu, Bálint/0000-0003-4024-116X; Kawaguchi, Atsushi/0000-0002-5485-1578; Nagata, Kyosuke/0000-0003-2522-3561; Gyurcsik, Béla/0000-0003-1894-7414}
}

@article{MTMT:33657316,
	title = {Chronic Cerebral Hypoperfusion-Induced Disturbed Proteostasis of Mitochondria and MAM Is Reflected in the CSF of Rats by Proteomic Analysis},
	url = {https://m2.mtmt.hu/api/publication/33657316},
	author = {Tukacs, Vanda and Mittli, Dániel Árpád and Hunyadi-Gulyás Éva, Csilla and Hlatky, Dávid and Medzihradszky F., Katalin and Darula, Zsuzsanna and Nyitrai, Gabriella and Czurkó, András and Juhász, Gábor Dénes and Kardos, József and Kékesi, Adrienna Katalin},
	doi = {10.1007/s12035-023-03215-z},
	journal-iso = {MOL NEUROBIOL},
	journal = {MOLECULAR NEUROBIOLOGY},
	volume = {60},
	unique-id = {33657316},
	issn = {0893-7648},
	abstract = {Declining cerebral blood flow leads to chronic cerebral hypoperfusion which can induce neurodegenerative disorders, such as vascular dementia. The reduced energy supply of the brain impairs mitochondrial functions that could trigger further damaging cellular processes. We carried out stepwise bilateral common carotid occlusions on rats and investigated long-term mitochondrial, mitochondria-associated membrane (MAM), and cerebrospinal fluid (CSF) proteome changes. Samples were studied by gel-based and mass spectrometry-based proteomic analyses. We found 19, 35, and 12 significantly altered proteins in the mitochondria, MAM, and CSF, respectively. Most of the changed proteins were involved in protein turnover and import in all three sample types. We confirmed decreased levels of proteins involved in protein folding and amino acid catabolism, such as P4hb and Hibadh in the mitochondria by western blot. We detected reduced levels of several components of protein synthesis and degradation in the CSF as well as in the subcellular fractions, implying that hypoperfusion-induced altered protein turnover of brain tissue can be detected in the CSF by proteomic analysis.},
	year = {2023},
	eissn = {1559-1182},
	pages = {3158-3174},
	orcid-numbers = {Czurkó, András/0000-0002-1985-7296; Juhász, Gábor Dénes/0000-0002-0849-6931; Kardos, József/0000-0002-2135-2932; Kékesi, Adrienna Katalin/0000-0003-3042-4878}
}

@article{MTMT:33609750,
	title = {Interactions of an Artificial Zinc Finger Protein with Cd(II) and Hg(II): Competition and Metal and DNA Binding},
	url = {https://m2.mtmt.hu/api/publication/33609750},
	author = {Hajdu, Bálint and Hunyadi-Gulyás Éva, Csilla and Gyurcsik, Béla},
	doi = {10.3390/inorganics11020064},
	journal-iso = {INORGANICS},
	journal = {INORGANICS},
	volume = {11},
	unique-id = {33609750},
	abstract = {Cys2His2 zinc finger proteins are important for living organisms, as they—among other functions—specifically recognise DNA when Zn(II) is coordinated to the proteins, stabilising their ββα secondary structure. Therefore, competition with other metal ions may alter their original function. Toxic metal ions such as Cd(II) or Hg(II) might be especially dangerous because of their similar chemical properties to Zn(II). Most competition studies carried out so far have involved small zinc finger peptides. Therefore, we have investigated the interactions of toxic metal ions with a zinc finger proteins consisting of three finger units and the consequences on the DNA binding properties of the protein. Binding of one Cd(II) per finger subunit of the protein was shown by circular dichroism spectroscopy, fluorimetry and electrospray ionisation mass spectrometry. Cd(II) stabilised a similar secondary structure to that of the Zn(II)-bound protein but with a slightly lower affinity. In contrast, Hg(II) could displace Zn(II) quantitatively (logβ′ ≥ 16.7), demolishing the secondary structure, and further Hg(II) binding was also observed. Based on electrophoretic gel mobility shift assays, the Cd(II)-bound zinc finger protein could recognise the specific DNA target sequence similarly to the Zn(II)-loaded form but with a ~0.6 log units lower stability constant, while Hg(II) could destroy DNA binding completely.},
	year = {2023},
	eissn = {2304-6740},
	orcid-numbers = {Gyurcsik, Béla/0000-0003-1894-7414}
}