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1.
Int J Mol Sci ; 22(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205737

RESUMO

3-bromopuryvate (3-BP) is a compound with unique antitumor activity. It has a selective action against tumor cells that exhibit the Warburg effect. It has been proven that the action of 3-BP is pleiotropic: it acts on proteins, glycolytic enzymes, reduces the amount of ATP, induces the formation of ROS (reactive oxygen species), and induces nuclear DNA damage. Mitochondria are important organelles for the proper functioning of the cell. The production of cellular energy (ATP), the proper functioning of the respiratory chain, or participation in the production of amino acids are one of the many functions of mitochondria. Here, for the first time, we show on the yeast model that 3-BP acts in the eukaryotic cell also by influence on mitochondria and that agents inhibiting mitochondrial function can potentially be used in cancer therapy with 3-BP. We show that cells with functional mitochondria are more resistant to 3-BP than rho0 cells. Using an MTT assay (a colorimetric assay for assessing cell metabolic activity), we demonstrated that 3-BP decreased mitochondrial activity in yeast in a dose-dependent manner. 3-BP induces mitochondrial-dependent ROS generation which results in ∆sod2, ∆por1, or ∆gpx1 mutant sensitivity to 3-BP. Probably due to ROS mtDNA lesions rise during 3-BP treatment. Our findings may have a significant impact on the therapy with 3-BP.


Assuntos
Antineoplásicos/farmacologia , DNA Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Piruvatos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae
2.
Biology (Basel) ; 10(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199665

RESUMO

Most underground ecosystems are heterotrophic, fungi in these objects are dispersed in the air in the form of spores, and they may be potentially hazardous to mammals. Research in underground sites has focused on mesophilic airborne fungi and only a few concerned cold-adapted species. Therefore, the goal of our research was the first report of psychrophilic and psychrotolerant aeromycota in the Brestovská Cave using culture-based techniques with genetic and phenotypic identification. Plates with PDA medium containing sampled biological material were incubated at 8 ± 0.5 °C. The density of mycobiota inside the cave ranged from 37.4 to 71 CFU 1 m-3 of air and 63.3 CFU 1 m-3 of air outside the cave. Thus, the level of fungal spores did not exceed the standards for the mycological quality of the air. A total of 18 species were isolated during the study, and some species may be potentially dangerous to people with weakened immune system. All fungal species were present inside the cave and only seven of them were outside. Cladosporium cladosporioides dominated in the external air samples and Mortierella parvispora was cultured most frequently from internal air samples. To our knowledge, this is the first discovery of the fungal species such as Coniothyrium pyrinum, Cystobasidium laryngis, Filobasidium wieringae, Leucosporidium drummii, M. parvispora, Mrakia blollopis, Nakazawaea holstii, and Vishniacozyma victoriae in the air inside the underground sites. Moreover, C. pyrinum, C. laryngis, L. drummii, M. blollopis, and N. holstii have never been detected in any component of the underground ecosystems. There are possible reasons explaining the detection of those species, but global warming is the most likely.

3.
Plants (Basel) ; 9(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271933

RESUMO

Epicoccum nigrum Link is a cosmopolitan species, and it has been described as both an in vitro and in vivo antagonist of many fungal pathogens of plants. However, there are no clear reports about the interactions between E. nigrum and various plant species, and about the effects of culture filtrates produced by this fungus on plants. Therefore, we assessed the interactions between E. nigrum and different plant species, such as sugar beet (Beta vulgaris L. ssp. vulgaris), spring wheat (Triticum aestivum L.), red clover (Trifolium pratense L.), and winter oilseed rape (Brassica napus L.). Additionally, we evaluated the effect of E. nigrum culture filtrates on garden cress (Lepidium sativum L.). Our study showed that the E. nigrum strains varied in terms of the color of excreted culture filtrates and showed different interactions with garden cress. Overall, fungal strains only affected adversely the sprout length in a significant way and, partially, the growth of the tested plant. In addition, we confirmed the suitability of the garden cress as a test plant in in vitro toxicological tests. Most strains of E. nigrum (61.1%) secreted enzymes expected to participate mainly in the later stages of the infection (amylases and proteases) and not those expected to operate in the early phases of host penetration (cellulases and pectinases) that were secreted by 33.3% of fungal strains. The group of pectinolytic enzymes represented the catalysts with the highest activity. Host specialization tests showed that E. nigrum was mainly re-isolated from the plant surface and the number of infected seedlings as well as the disease index depended on a studied plant species, with sugar beet and red clover being most sensitive to infection. In turn, the lowest value of the disease index caused by E. nigrum strains was recorded for spring wheat and winter oilseed rape. Overall, statistically significant differences in the growth of plant seedlings during the host specialization test were noted only for sugar beet and red clover seedlings. The seedlings of plants in the control group (without fungal inoculum) exhibited an increased length compared to those treated with E. nigrum inoculum. Our studies also showed that E. nigrum is probably a facultative saprotroph of plants and it may winter on red clover, which is presumably its main reservoirs, among the species considered.

4.
Animals (Basel) ; 10(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756314

RESUMO

Bats play important functions in ecosystems and many of them are threatened with extinction. Thus, the monitoring of the health status and prevention of diseases seem to be important aspects of welfare and conservation of these mammals. The main goal of the study was the identification of culturable fungal species colonizing the wing membranes of female greater mouse-eared bat (Myotis myotis) during spring emergence from the "Nietoperek" underground hibernation site by the use of genetic and phenotypic analyses. The study site is situated in Western Poland (52°25' N, 15°32' E) and is ranked within the top 10 largest hibernation sites in the European Union. The number of hibernating bats in the winter exceeds 39,000 individuals of 12 species, with M. myotis being the most common one. The wing membranes of M. myotis were sampled using sterile swabs wetted in physiological saline (0.85% NaCl). Potato dextrose agar (PDA) plates were incubated in the dark at 8, 24 and 36 ± 1 °C for 3 up to 42 days. All fungi isolated from the surface of wing membranes were assigned to 17 distinct fungal isolates belonging to 17 fungal species. Penicillium chrysogenum was the most frequently isolated species. Some of these fungal species might have a pathogenic potential for bats and other mammals. However, taking into account habitat preferences and the life cycle of bats, it can be assumed that some fungi were accidentally obtained from the surface of vegetation during early spring activity. Moreover, Pseudogymnoascus destructans (Pd)-the causative agent of the White Nose Syndrome (WNS)-was not found during testing, despite it was found very often in M. myotis during previous studies in this same location.

5.
J Inorg Biochem ; 210: 111124, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32534287

RESUMO

Biological activity against reference and multi-drug resistant (MDR) clinical strains of fluoroquinolones (FQs): ciprofloxacin (HCp), norfloxacin (HNr), lomefloxacin (HLm) and sparfloxacin (HSf), phosphine ligands derived from those antibiotics and 14 phosphino copper(I) and copper(II) complexes with 2,9-dimethyl-1,10-phenanthroline, 1,10-phenanthroline or 2,2'-biquinoline have been determined. Almost all phosphines showed excellent antibacterial activity relative to reference strains (S. aureus ATCC 6538, E. coli ATCC 25922, K. pneumoniae ATCC 4352, and P. aeruginosa ATCC 27853). In rare cases P. aeruginosa rods showed natural insensitivity to oxides, and their copper(II) complexes. Most of the studied compounds showed weak antibacterial activity against clinical multi-drug resistant strains (MDR P. aeruginosa 16, 46, 325, 355, MRD A. baumanii 483 and MDR S. aureus 177). However, phosphines Ph2PCH2Sf (PSf), Ph2PCH2Lm (PLm) and their copper(I) complexes were characterized by the best antibacterial activity. In addition, PSf compounds, in which the activities relative to P. aeruginosa MDRs were relatively diverse, paid particular attention in our studies. Genetic and phenotypic studies of these strains showed significant differences between the strains, indicating different profiles of FQs resistance mechanisms. This may prove that a change in the spatial conformation of the PSf derivatives relative to the native form of HSf increased its affinity for the target site of action in gyrase, leading to selective inhibition of the multiplication of MDR strains. In conclusion, differences in PSf activity within closely related P. aeruginosa strains may indicate its diagnostic and therapeutic potential.


Assuntos
Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia , Fluoroquinolonas/farmacologia , Fosfinas/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Complexos de Coordenação/química , Cobre/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fluoroquinolonas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fosfinas/química , Relação Estrutura-Atividade
6.
Cells ; 9(5)2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397119

RESUMO

3-bromopyruvate (3-BP) is a small molecule with anticancer and antimicrobial activities. 3-BP is taken up selectively by cancer cells' mono-carboxylate transporters (MCTs), which are highly overexpressed by many cancers. When 3-BP enters cancer cells it inactivates several glycolytic and mitochondrial enzymes, leading to ATP depletion and the generation of reactive oxygen species. While mechanisms of 3-BP uptake and its influence on cell metabolism are well understood, the impact of 3-BP at certain concentrations on DNA integrity has never been investigated in detail. Here we have collected several lines of evidence suggesting that 3-BP induces DNA damage probably as a result of ROS generation, in both yeast and human cancer cells, when its concentration is sufficiently low and most cells are still viable. We also demonstrate that in yeast 3-BP treatment leads to generation of DNA double-strand breaks only in S-phase of the cell cycle, possibly as a result of oxidative DNA damage. This leads to DNA damage, checkpoint activation and focal accumulation of the DNA response proteins. Interestingly, in human cancer cells exposure to 3-BP also induces DNA breaks that trigger H2A.X phosphorylation. Our current data shed new light on the mechanisms by which a sufficiently low concentration of 3-BP can induce cytotoxicity at the DNA level, a finding that might be important for the future design of anticancer therapies.


Assuntos
Antineoplásicos/farmacologia , Dano ao DNA , Piruvatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla , Reparo do DNA/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Recombinação Homóloga/genética , Humanos
7.
Methods Mol Biol ; 2049: 389-402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602623

RESUMO

The dramatic increase of cancer in the world drives the search for a new generation of drugs useful in effective and safe chemotherapy. In the postgenomic era the use of the yeast Saccharomyces cerevisiae as a simple eukaryotic model is required in molecular studies of biological activity of compounds that may be potential drugs in the future. The phenotype analysis of numerous deletion mutants (from the EUROSCARF collection) allows one to define the specific influence of tested compound on metabolism, stress generation and response of eukaryotic cell to stress. Moreover, it allows one to determine cell viability, design of new drugs and doses used in preclinical and clinical trials. Undoubtedly, this is also a good way to save the lives of many laboratory animals. Here we present a simple and cheap new approach to study the metabolic and stress response pathways in eukaryotic cells involved in the response to tested compounds (e.g., anticancer agents). The precise determination of biological activity mechanisms of tested compounds at the molecular level can contribute to the fast introduction of new cancer therapies, which is extremely important nowadays.


Assuntos
Antineoplásicos/farmacologia , Genoma Fúngico/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Metabolismo Energético/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Mutação , Saccharomyces cerevisiae/genética
8.
J Inorg Biochem ; 189: 69-80, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30243120

RESUMO

Fusobacterium nucleatum is an anaerobic, Gram-negative bacteria linked to colon cancer. It is interesting to determine how metal ions interact with bacterial adhesin proteins. To this end, the coordination of ATDAAS-NH2 and MKKFL-NH2 fragments of Fusobacterium adhesin A (FadA) to copper(II) ions was studied by potentiometry, spectroscopic techniques (UV-Vis, CD, EPR and NMR) and the density functional theory (DFT) methods. At pH 6.8 (colon physiological pH), the metal ion in the first peptide (ATDAAS-NH2) is coordinated by one oxygen and three nitrogen donors while in the second one (MKKFL-NH2) - by sulfur and three nitrogen atoms. Both complexes form two five- and one six-membered stable chelate rings. Moreover, reactivity studies confirmed the production of reactive oxygen species such as hydroxyl radical, superoxide anion radical and singlet oxygen. Generation of reactive oxygen species (ROS) was observed during gel electrophoresis and spectroscopic assays with reporting molecules like NDMA (N,N-dimethyl-p-nitrosoaniline) and NBT (Nitrotetrazolium Blue Chloride). All reactions were conducted in the presence of hydrogen peroxide as endogenous oxidant.


Assuntos
Adesinas Bacterianas/química , Cobre/química , Fusobacterium nucleatum/química , Espectroscopia de Ressonância de Spin Eletrônica , Concentração de Íons de Hidrogênio , Potenciometria , Espécies Reativas de Oxigênio/química , Superóxidos/química
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