Papers by Laszlo Csernoch
Journal of Basic Microbiology, Jul 21, 2011
The β-lactam producing filamentous fungus Penicillium chrysogenum secretes a 6.25 kDa small molec... more The β-lactam producing filamentous fungus Penicillium chrysogenum secretes a 6.25 kDa small molecular mass antifungal protein, PAF, which has a highly stable, compact 3D structure and is effective against a wide spectrum of plant and zoo pathogenic fungi. Its precise physiological functions and mode of action need to be elucidated before considering possible biomedical, agricultural or food technological applications. According to some more recent experimental data, PAF plays an important role in the fine-tuning of conidiogenesis in Penicillium chrysogenum. PAF triggers apoptotic cell death in sensitive fungi, and cell death signaling may be transmitted through two-component systems, heterotrimeric G protein coupled signal transduction and regulatory networks as well as via alteration of the Ca(2+) -homeostasis of the cells. Possible biotechnological applications of PAF are also outlined in the review.
Biophysical Journal, Feb 1, 2016
PubMed, 1999
In striated muscle contraction is under the tight control of myoplasmic calcium concentration ([C... more In striated muscle contraction is under the tight control of myoplasmic calcium concentration ([Ca2+]i): the elevation in [Ca2+]i and the consequent binding of calcium to troponin C enables, while the decrease in [Ca2+]i prevents the actin-myosin interaction. Calcium ions at rest are stored in the sarcoplasmic reticulum (SR) from which they are rapidly released upon the depolarisation of the sarcolemmal and transverse (T-) tubular membranes of the muscle cell. The protein responsible for this controlled and fast release of calcium is the calcium release channel found in the membrane of the terminal cisternae of the SR. This review focuses on the physiological and pharmacological modulators of the calcium release channel and tries to draw an up-to-date picture of the events that occur between T-tubular depolarisation and the release of calcium from the SR.
Expert Opinion on Therapeutic Targets, Oct 30, 2018
Introduction: Diseases caused by pathogenic fungi are increasing because of antibiotic overuse, t... more Introduction: Diseases caused by pathogenic fungi are increasing because of antibiotic overuse, the rise of immunosuppressive therapies and climate change. The limited variety of antimycotics and the rapid adaptation of pathogenic fungi to antifungal agents serve to exacerbate this issue. Unfortunately, about 1.6 million people globally are killed by fungal infections on a yearly basis. The discovery of the small antimicrobial proteins produced by microorganisms, animals, humans and plants will hopefully overcome challenges in the treatment of fungal infections. These small proteins are highly stable and any resistance to them rarely evolves; therefore, they are potentially good candidates for the treatment and prevention of infections caused by pathogenic fungi. Some of these proteins target the programmed cell death machinery of pathogenic fungi; this is potentially a novel approach in antimycotic therapies. In this review, we highlight the elements of apoptosis in human pathogenic fungi and related model organisms and discuss the possible therapeutic potential of the apoptosis-inducing, small, antifungal proteins. Expert opinion: Small antimicrobial proteins may establish a new class of antimycotics in the future. The rarity of resistance and their synergistic effects with other frequently used antifungal agents may help pave the way for their use in the clinic.
Toxins, Nov 28, 2021
The intensifying world-wide spread of mycotoxigenic fungal species has increased the possibility ... more The intensifying world-wide spread of mycotoxigenic fungal species has increased the possibility of mycotoxin contamination in animal feed and the human food chain. Growing evidence shows the deleterious toxicological effects of mycotoxins from infants to adults, while large population-based screening programs are often missing to identify affected individuals. The kidney functions as the major excretory system, which makes it particularly vulnerable to nephrotoxic injury. However, few studies have attempted to screen for kidney injury biomarkers in large, mycotoxinexposed populations. As a result, there is an urgent need to screen them with sensitive biomarkers for potential nephrotoxicity. Although a plethora of biomarkers have been tested to estimate the harmful effects of a wide spectrum of toxicants, β 2 -microglobulin (β 2 -MG) and N-acetyl-β-D-glucosaminidase (NAG) are currently the dominant biomarkers employed routinely in environmental toxicology research. Nevertheless, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as useful and informative markers to reveal mycotoxin induced nephrotoxicity. In this opinion article we consider the nephrotoxic effects of mycotoxins, the biomarkers available to detect and quantify the kidney injuries caused by them, and to recommend biomarkers to screen mycotoxin-exposed populations for renal damage.
Biocontrol, Dec 21, 2016
Today's dearth of effective antimicrobial agents can be overcome by the use of antimicrobial prot... more Today's dearth of effective antimicrobial agents can be overcome by the use of antimicrobial proteins, which are produced naturally by a wide range of organisms including microorganisms, plants and mammals. These small basic proteins are highly stable, easy to manufacture on a large scale, and any resistance against them develops only rarely. These proteins are therefore good candidates for the treatment and prevention of various fungal infections. Importantly, these protein-based antimycotics can even be expressed heterologously in suitable organisms and can be used for various agricultural purposes in the future including biocontrol applications. In this review, we summarize today's knowledge on the sources, structures, large-scale productions, direct surface applications as well as on the heterologous expressions in host plants of the small molecular mass antifungal proteins produced by filamentous fungi. Future developments foreseeable in this promising area of antifungal protein research are also presented and discussed in this review.
Acta Physiologica Hungarica, Sep 1, 2014
Evaluation of voice quality parameters of esophageal speech in different neoglottis forms after t... more Evaluation of voice quality parameters of esophageal speech in different neoglottis forms after total laryngectomy. Methods: Presentation of voice analysis of 20 patients, who underwent total laryngectomy. The success of acquiring this technique was estimated by means of a voice analyzing program (pitch, sound-holding, loudness, spectrogram), and by the intelligibility via the telephone. Shape of the different types of neoglottis that developed and its functioning during vocalization and continuous speech were observed by nasal endoscopy. Data obtained from the voice analysis were compared among the observed three different neoglottis forms. Results: The average dysphonia index of the 20 patients was 1.67 ± 0.38 (mean ± SD). Nasal fiberoscopic examination revealed three different types of neoglottis forms -a small mucosal button, two mucosal battens, and a mucosal lip. Voice quality of the esophageal speech of the patients with the mucosal button was found to be the closest to normal by subjective and objective acoustical evaluation. Conclusions: These findings emphasize the importance of the proper wound closure technique which can facilitate the development of a special button shape neoglottis form and help to acquire esophageal speech with the best quality parameters shortly after total laryngectomy.
Summary The effect of the chaotropic cation guanidinium on tension generation was investigated in... more Summary The effect of the chaotropic cation guanidinium on tension generation was investigated in voltage-clamped intact and mechanically skinned muscle fibres of the frog. When sodium was replaced by guanidinium in the solution a 20-mV shift of the sigmoidal activation curve towards less negative potentials was recorded. A similar shift in the voltage dependence of mechanical inactivation did not occur. The plateau phase of contractures activated by long-lasting depolarizations was significantly shortened in the presence of 77.5 mM guanidinium. In a second set of experiments, charge displacement currents were measured using the cut fibre preparation. Apparently, guanidinium had no effect on the voltage dependence of intramembrane charge movement. On the other hand, this cation caused a distinct increase in the amount of charge necessary to reach the contraction threshold at rheobase voltage from 12.4 nC ~F -1 to 23.4 nC ~F -1. Experiments on skinned fibres containing an operating sarcoplasmic reticulum demonstrated that 5 mM guanidinium diminished caffeine-induced tension development and substantially delayed the onset of the contractile response. However, guanidinium did not impair calcium-induced tension development of the contractile apparatus. These results suggest that the inhibitory action of guanidinium on excitation-contraction coupling is due to a depression of calcium release from the sarcoplasmic reticulum.
Toxicological Sciences, Mar 4, 2019
Acta Medicinae et Sociologica, 2020
Számos kutatás bizonyította, hogy a hosszútávfutást sajnos számos átmeneti, kedvezőtlen hatás is ... more Számos kutatás bizonyította, hogy a hosszútávfutást sajnos számos átmeneti, kedvezőtlen hatás is kíséri, melyek közül a legfontosabbak a vesét, a mozgásszerveket, valamint a szív- és érrendszert, illetve a gasztrointesztinális traktust érintő, káros hatások voltak. Orvosi szempontból lényeges lenne ezeknek a kedvezőtlen hatásoknak a megelőzése, enyhítése, illetve modulálása. A testedzés okozta károsodások élettani és immunológiai hátterének pontosabb megértése érdekében 8 egészséges, edzett, önkéntes férfi alanyon végeztek egy tanulmányt, melyben egy 2 órás protokollt követtek. Ez a protokoll 1 óra intenzív kerékpározást, valamint 1 óra intenzív futást foglalt magába, folyamatos orvosi ellenőrzés mellett, kontrollált körülmények között. A vizsgálatok a futók klinikai kémiai paraméterei változásának, illetve a neutrofil granulocitákban lezajló globális génexpresszió változásoknak a leírására összpontosulnak. Ezeket a vizsgálatokat közvetlenül a fizikai terhelés előtt („baseline”), il...
Journal of Basic Microbiology, 2020
The P‐type ATPase CrpA is an important Cu2+/Cd2+ pump in the Aspergilli, significantly contributi... more The P‐type ATPase CrpA is an important Cu2+/Cd2+ pump in the Aspergilli, significantly contributing to the heavy metal stress tolerance of these ascomycetous fungi. As expected, the deletion of crpA resulted in Cu2+/Cd2+‐sensitive phenotypes in Aspergillus nidulans on stress agar plates inoculated with conidia. Nevertheless, paradoxical growth stimulations were observed with the ΔcrpA strain in both standard Cu2+ stress agar plate experiments and cellophane colony harvest (CCH) cultures, when exposed to Cd2+. These observations reflect efficient compensatory mechanisms for the loss of CrpA operating under these experimental conditions. It is remarkable that the ΔcrpA strain showed a 2.7 times higher Cd biosorption capacity in CCH cultures, which may facilitate the development of new, fungal biomass‐based bioremediation technologies to extract harmful Cd2+ ions from the environment. The nullification of crpA also significantly changed the spatial distribution of Cu and Cd in CCH cult...
Environmental Technology, 2020
The fungus Aspergillus oryzae could be shown to be a viable alternative for biosorption of valuab... more The fungus Aspergillus oryzae could be shown to be a viable alternative for biosorption of valuable metals from solution. Fungal biomass can be obtained easily in high quantities as a waste of biofermentation processes, and used in a complex, multi-phase solution mimicking naturally occurring, mining-affected water samples. With test solution formulated after natural conditions, formation of secondary Al and Fe phases co-precipitating Ce was recorded in addition to specific biosorption of rare earth elements. Remarkably, the latter were removed from the solution despite the presence of high concentrations of interfering Fe and Al. The biomass was viable even after prolonged incubation in the metal solution, and minimal inhibitory concentrations for single metals were higher than those in the test solution. While precipitation/biosorption of Ce (maximal biosorption efficiency was 58.0 ±22.3 % after 6 h of incubation) coincided with the gross removal of Fe from the metal solution, Y (81.5 ±11.3 % efficiency, 24 h incubation) and Nd (87.4 ±9.1 % efficiency, 24 h incubation) were sequestered later, similarly to Ni and Zn. The biphasic binding pattern specific to single metals could be connected to dynamically changing pH and NH4 + concentrations, which were attributed to the physiological changes taking place in starving A. oryzae biomass. The metals were found extracellularly in minerals associated with the cell wall, and intracellularly precipitated in the vacuoles. The latter process was explained with intracellular metal detoxification resulting in metal resistance. Aspergillus oryzae mycelia captured Y and Nd from a complex, multi-phase test solution concomitantly with increasing pH and NH4 + ion concentrations. Changing fungal cell physiology in starving mycelia may help to develop new technologies to sequester precious rare earth elements including Y effectively, even in the presence of high concentrations of interfering metals like Fe and Al.
Pathology oncology research : POR, Jan 18, 2016
Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warbur... more Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124. Significant relationships have been confirmed between the levels of SIRT6, HDAC4 and the microRNAs listed above. In NPM1-mutated AML (n = 6), the level of miR-125b was significantly lower than in the group of AML patients not carrying this mutation (n = 13) (p < 0.05). In M5 FAB type of AML (n = 5), the level of miR-124 was significantly higher compare...
Frontiers in Immunology, 2013
Molecular Cancer, 2014
Introduction: Ras guanine nucleotide exchange factors (RasGEFs) mediate the activation of the Ras... more Introduction: Ras guanine nucleotide exchange factors (RasGEFs) mediate the activation of the Ras signaling pathway that is over activated in many human cancers. The RasGRP3, an activator of H-Ras and R-Ras protein exerts oncogenic effects and the overexpression of the protein is observed in numerous malignant cancer types. Here, we investigated the putative alteration of expression and potential function of RasGRP3 in the formation and progression of human breast cancer. Methods: The RasGRP3 and phosphoRasGRP3 expressions were examined in human invasive ductal adenocarcinoma derived samples and cell lines (BT-474, JIMT-1, MCF7, SK-BR-3, MDA-MB-453, T-47D) both in mRNA (Q-PCR) and protein (Western blot; immunohistochemistry) levels. To explore the biological function of the protein, RasGRP3 knockdown cultures were established. To assess the role of RasGRP3 in the viability of cells, annexin-V/PI staining and MitoProbe™ DilC1 (5) assay were performed. To clarify the function of the protein in cell proliferation and in the development of chemotherapeutic resistance, CyQuant assay was performed. To observe the RasGRP3 function in tumor formation, the Severe combined immunodeficiency (SCID) mouse model was used. To investigate the role of the protein in Ras-related signaling Q-PCR and Western blot experiments were performed. Results: RasGRP3 expression was elevated in human breast tumor tissue samples as well as in multiple human breast cancer cell lines. Down-regulation of RasGRP3 expression in breast cancer cells decreased cell proliferation, induced apoptosis in MCF7 cells, and sensitized T-47D cells to the action of drugs Tamoxifen and trastuzumab (Herceptin). Gene silencing of RasGRP3 reduced tumor formation in mouse xenografts as well. Inhibition of RasGRP3 expression also reduced Akt, ERK1/2 and estrogen receptor alpha phosphorylation downstream from IGF-I insulin like growth factor-I (IGF-I) or epidermal growth factor (EGF) stimulation confirming the functional role of RasGRP3 in the altered behavior of these cells. Conclusions: Taken together, our results suggest that the Ras activator RasGRP3 may have a role in the pathological behavior of breast cancer cells and may constitute a therapeutic target for human breast cancer.
Nature Communications, Mar 10, 2023
During muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transc... more During muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transcription of Myocyte-specific Enhancer Factor 2 (Mef2D). Sequence analysis by the FuzDrop method indicates that the β-domain can serve as an interaction element for Mef2D higher-order assembly. In accord, we observed Mef2D mobile nuclear condensates in C2C12 cells, similar to those formed through liquid-liquid phase separation. In addition, we found Mef2D solid-like aggregates in the cytosol, the presence of which correlated with higher transcriptional activity. In parallel, we observed a progress in the early phase of myotube development, and higher MyoD and desmin expression. In accord with our predictions, the formation of aggregates was promoted by rigid β-domain variants, as well as by a disordered β-domain variant, capable of switching between liquid-like and solid-like higher-order states. Along these lines, NMR and molecular dynamics simulations corroborated that the β-domain can sample both ordered and disordered interactions leading to compact and extended conformations. These results suggest that β-domain fine-tunes Mef2D higher-order assembly to the cellular context, which provides a platform for myogenic regulatory factors and the transcriptional apparatus during the developmental process. Myogenic lineage establishment and maintenance of terminal myogenic phenotype is controlled by precise dynamics of temporal and spatial expression, and hierarchical relationship between four myogenic regulatory factors (MRFs) 1 . Myocyte-specific Enhancer Factor 2 (Mef2) protein belongs to the MADS (MCM1-Agamous-Deficiensserum response factor) box family of transcription factors, which potentiate the transcriptional activity of myogenic proteins 2 . Mef2 activity is precisely controlled during muscle development;
Journal of Muscle Research and Cell Motility, Dec 10, 2021
Making benefit from the epigenetic effects of environmental factors such as physical activity may... more Making benefit from the epigenetic effects of environmental factors such as physical activity may result in a considerable improvement in the prevention of chronic civilization diseases. In our chronic swimming rat model, the expression levels of such microRNAs were characterized, that are involved in skeletal muscle differentiation, hypertrophy and fine-tuning of metabolism, which processes are influenced by chronic endurance training, contributing to the metabolic adaptation of skeletal muscle during physical activity. After chronic swimming, the level of miR-128a increased significantly in EDL muscles, which may influence metabolic adaptation and stress response as well. In SOL, the expression level of miR-15b and miR-451 decreased significantly after chronic swimming, which changes are opposite to their previously described increment in insulin resistant skeletal muscle. MiR-451 also targets PGC-1α mRNA, whiches expression level significantly increased in SOL muscles, resulting in enhanced biogenesis and oxidative capacity of mitochondria. In summary, the microRNA expression changes that were observed during our experiments suggest that chronic swim training contributes to a beneficial metabolic profile of skeletal muscle.
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Papers by Laszlo Csernoch