Erdostein belongs to the well-known thiol mucoactive drugs, whose effect is used in respiratory infections. Recently, expert findings show that the effect of erdosteine is more complex and can significantly contribute to the management of respiratory infections. Its antioxidant and anti-inflammatory properties come to the fore, or antiviral properties associated with them, as well as the ability to reduce bacterial adhesion and increase the effects of some antibiotics. Erdostein represents a comprehensive therapeutic option both in the field of self-treatment of respiratory infections and in other respiratory diseases.
- Klíčová slova
- erdostein, mucomodulation, respiratory disease,
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- antiflogistika farmakologie terapeutické užití MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- expektorancia * terapeutické užití farmakologie MeSH
- infekce dýchací soustavy farmakoterapie MeSH
- lidé MeSH
- thiofeny * farmakologie terapeutické užití MeSH
- thioglykoláty * farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antibakteriální látky MeSH
- antiflogistika MeSH
- antioxidancia MeSH
- antivirové látky MeSH
- erdosteine MeSH Prohlížeč
- expektorancia * MeSH
- thiofeny * MeSH
- thioglykoláty * MeSH
BACKGROUND: Mammalian metallothioneins (MTs) play a crucial role in maintaining Zn(II) and Cu(I) homeostasis, as well as regulating the cellular redox potential. They are involved in cancer resistance to cisplatin-related drugs and the sequestration of toxic metal ions. To investigate their participation in specific physiological and pathological processes, it is imperative to develop an analytical method for measuring changes in protein concentration both in vitro and in vivo. Over the years, numerous methods have been developed for this purpose; however, they often suffer from issues such as low sensitivity, lengthy sample preparation, or variability in antibody batches. RESULTS: In this study, we present, for the first time, the application of the fluorescent biarsenical probe CrAsH-EDT2 for the specific and ultrasensitive detection of human MTs. The interaction between the small library of biarsenical probes and 11 human MT isoforms (MT1-MT4), isolated MT2 domains, snail LlMT, and plant phytochelatin PC4 was investigated using spectrofluorimetry and mass spectrometry. A key advantage of our method is that the probe excess does not need to be removed before measurement as unbound is virtually non-fluorescent. We established protocols for MT detection in various assays, including cuvette-based, SDS-PAGE, and capillary electrophoresis. A detection limit (LOD) of 100 fg for human MT2 was achieved. Finally, we observed increased metallothionein concentration in lysates of HeLa cells treated with ZnSO4. SIGNIFICANCE: In conclusion, our results demonstrate that the established method is easy to apply, versatile, and can be adapted to detect metallothioneins and other poly-Cys targets in different assays and applications.
- Klíčová slova
- Biarsenical probe, Bioassay, Metallothionein, Phytochelatin, Protein concentration,
- MeSH
- cystein metabolismus analýza chemie MeSH
- fluorescenční barviva * chemie MeSH
- fluorescenční spektrometrie MeSH
- lidé MeSH
- limita detekce MeSH
- metalothionein * metabolismus analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cystein MeSH
- fluorescenční barviva * MeSH
- metalothionein * MeSH
The acidobasic and complexing properties of 1-methyl-2-mercaptoimidazole (Methimazole, an anti-thyroid drug) were investigated. The pKa 11.49 ± 0.03 was estimated by molecular absorption spectroscopy (I = 0.10 M NaCl, t = 25.0 ± 0.1 °C). This value is in good agreement with the value 11.58 ± 0.05, obtained using the solvent-extraction technique. Theoretical (LFER and quantum chemical calculations) and experimental (1H/13C NMR spectroscopy) methods confirmed that the ligand prefers to be in the thion form, and the proton dissociation takes place on the nitrogen atom. Using glass electrode potentiometry, the complexation of the Pd(II) ion by the methimazole ligand occurs without the participation of protons. The best chemical model considers the [Pd(HL)]2+, [Pd(HL)2]2+ and [Pd(HL)3]2+ complex species, whose stability constants were also determined using spectroscopy and capillary zone electrophoretic (CZE) measurements. The metal complexes dissociate at -log [H+] > 7, where an uncharged palladium(II) hydroxide is formed. The formation kinetics of the palladium(II) complex with methimazole were studied in perchloric and hydrochloric acids (I = 1.00 M, t = 15-40 °C) and the determined rate constants and activation parameters are consistent with literature values determined for the reactions of the Pd(II) ion with thiourea derivatives. The rate constants decrease by two orders of magnitude in both media, which can be assigned to a lower tendency of the chloride ion to dissociate from the [PdCl4]2- complex species than the water molecule from the [Pd(H2O)4]2+ ion. The presented results can be utilized for the design of new Pd and Pt metallodrugs.
- Klíčová slova
- Anti-thyroid drug (methimazol, tapazol): 1-methyl-2-mercaptoimidazole, Complexation properties, Equilibria/kinetics, Metallodrug, Pd(II) ion, Protonation,
- MeSH
- kinetika MeSH
- komplexní sloučeniny * chemie chemická syntéza MeSH
- methimazol * chemie MeSH
- palladium * chemie MeSH
- termodynamika * MeSH
- thyreostatika chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- komplexní sloučeniny * MeSH
- methimazol * MeSH
- palladium * MeSH
- thyreostatika MeSH
Intensive agricultural practices impact the health and nutrition of pollinators like honey bees (Apis mellifera). Rapeseed (Brassica napus L.) is widely cultivated, providing diverse nutrients and phytochemicals, including S-methyl-L-cysteine sulfoxide (SMCSO). While the nutritional impact of rapeseed on bees is known, SMCSO's effects remain unexplored. We examined SMCSO and its related metabolites-3-methylthiolactic acid sulfoxide and N-acetyl-S-methyl-L-cysteine sulfoxide-analysing their seasonal fluctuations, colony variations and distribution in body parts. Our findings showed that these compounds in bee gut vary among colonies, possibly due to the dietary preferences, and are highly concentrated in bodies during the summer. They are distributed differently within bee bodies, with higher concentrations in the abdomens of foragers compared with nurses. Administration of SMCSO in a laboratory setting showed no immediate toxic effects but significantly boosted bees' antioxidant capacity. Long-term administration decreased bee body weight, particularly in the thorax and head, and altered amino acid metabolism. SMCSO is found in the nectar and pollen of rapeseed flowers and highly accumulates in rapeseed honey compared with other types of honey. This study reveals the dual impact of SMCSO on bee health, providing a basis for further ecological and physiological research to enhance bee health and colony sustainability.
- Klíčová slova
- Apis mellifera, Brassicaceae, S-methyl-L-cysteine sulfoxide, phytochemical, rapeseed, toxicity,
- MeSH
- antioxidancia farmakologie MeSH
- Brassica napus metabolismus MeSH
- Brassicaceae chemie MeSH
- cystein * analogy a deriváty metabolismus MeSH
- fytonutrienty farmakologie MeSH
- med analýza MeSH
- opylení MeSH
- pyl chemie MeSH
- roční období MeSH
- včely účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia MeSH
- cystein * MeSH
- fytonutrienty MeSH
Isolation and structural characterization of two large families of organosulfur compounds spontaneously formed upon cutting of onion (Allium cepa) were carried out. The structures of these hitherto unknown species, trivially named cepathiolactols and cepathiolactones, were established based on NMR, MS, and IR data. It was found that cepathiolactols (CxHyOS3 and CxHyO2S4; x = 7-12, y = 14-24) are 3,4-dimethyl-γ-thiolactols bearing various side chains linked via a disulfanyl moiety at position C-5. On the other hand, cepathiolactones were shown to be 3,4-dimethyl-γ-thiolactones structurally analogous to cepathiolactols. Sensory properties of cepathiolactols were also evaluated, along with testing their ability to participate in the formation of pink discoloration of processed onion.
- Klíčová slova
- Allium cepa, allithiolane, cepadithiolactone, cepaene, cepathiolactol, cepathiolactone, cepathiolane, isoalliin, onion, onionin, thiolane, thiosulfinate,
- MeSH
- česneky * chemie MeSH
- laktony chemie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární struktura MeSH
- rostlinné extrakty chemie MeSH
- sloučeniny síry * chemie MeSH
- sulfhydrylové sloučeniny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- laktony MeSH
- rostlinné extrakty MeSH
- sloučeniny síry * MeSH
- sulfhydrylové sloučeniny MeSH
Plant-specific receptor-like protein kinases (RLKs) are essential for pathogen recognition during pattern-triggered immunity. Together with coreceptors and associated proteins, they act as bona fide immune receptors, perceiving a variety of microbe-associated molecular patterns or damage-associated molecular patterns. The cysteine-rich receptor-like kinases (CRKs) form one of the biggest subgroups of RLKs, but so far, their ligands have not been identified. It has been shown that CRKs play important roles in plant immunity and defense responses as well as in response to abiotic stimuli and in control of plant development. However, molecular information on how CRKs integrate with the known framework of signaling components controlling early defense responses remains enigmatic.
- MeSH
- cystein metabolismus MeSH
- imunita rostlin * MeSH
- proteinkinasy * metabolismus genetika MeSH
- rostlinné proteiny metabolismus genetika MeSH
- rozpoznávání přirozenou imunitou MeSH
- signální transdukce MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cystein MeSH
- proteinkinasy * MeSH
- rostlinné proteiny MeSH
Biological thiols spontaneously form a stable Au-S dative bond with gold nanoparticles (AuNP) that might be used for their selective extraction and enrichment in biological samples. In this work, interactions of selected biological thiols (glutathione, cysteine, homocysteine [Hcys], cysteamine [CA], and N-acetylcysteine) with AuNP stabilized by different capping agents (citrate, Tween 20, Brij 35, CTAB, SDS) were investigated by UV-Vis spectroscopy and capillary electrophoresis with laser-induced fluorescence. Spectrophotometric measurements showed aggregation of Hcys and CA with AuNP. In contrast, it was confirmed by CE-LIF that biological thiols were adsorbed to all types of AuNP. Citrate-capped AuNP were selected for AuNP-based extraction of biological thiols from exhaled breath condensate (EBC). Dithiothreitol was utilized for desorption of biological thiols from the AuNP surface, which was followed by derivatization with eosin-5-maleimide and CE-LIF analysis. AuNP-based extraction increased the sensitivity of CE-LIF analysis; however, further optimization of methodology is necessary for accurate quantification of biological thiols in EBC.
- Klíčová slova
- CE‐LIF, biological thiols, exhaled breath condensate, extraction, gold nanoparticles,
- MeSH
- dechové testy metody MeSH
- elektroforéza kapilární * metody MeSH
- fluorescenční spektrometrie metody MeSH
- kovové nanočástice * chemie MeSH
- lidé MeSH
- sulfhydrylové sloučeniny * analýza chemie MeSH
- zlato * chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- sulfhydrylové sloučeniny * MeSH
- zlato * MeSH
The uptake of nickel (Ni) by Asteraceae/Cichorioideae species Cichorium intybus, Leontodon hispidus and Hieracium aurantiacum exposed to Ni (0.3 or 30 μM) over 14 days and subsequent changes of metabolites were compared in order to identify their phytoaccumulation potential. Hieracium contained the most Ni (194 and 1558 μg Ni/g DW at 30 μM Ni in shoots and roots) but had unchanged amount of antioxidants (vitamin C and thiols) in the shoots and an elevated amount in the roots, which may be the reason for the absence of visible damage. On the contrary, Leontodon reacted by a decrease in antioxidants to an excess of Ni, which can be related to enhanced oxidative stress (an increase in ROS and a decrease in nitric oxide detected by fluorescence microscopy). All roots were anatomically in the secondary state and Ni-induced cell wall thickening (i.e. lignin/suberin deposition) was most visible in Hieracium roots, which also contained 2-times more Ni than the other species. Among essential elements, mainly Fe accumulation was affected by Ni excess. The content of soluble phenols increased while organic acids (malic and citric) decreased sometimes extensively (up to 90%) in individual species. PCA analyses showed that especially ascorbic acid, thiols and phenols affect the separation in the shoots especially with regard to applied concentration of Ni, while these metabolites in the roots clearly separated the species (Cichorium from the others). The data show the highest tolerance to Ni in Hieracium, but the highest phytoaccumulation of Ni was found in Cichorium (626 μg Ni/plant or 122 μg Ni/shoot at a dose of 30 μM Ni).
- Klíčová slova
- Antioxidants, Bioaccumulation, Heavy metals, Phytoremediation, Reactive oxygen species,
- MeSH
- antioxidancia * metabolismus MeSH
- Asteraceae * metabolismus MeSH
- kořeny rostlin * metabolismus MeSH
- kyselina askorbová metabolismus MeSH
- látky znečišťující půdu metabolismus MeSH
- nikl * metabolismus MeSH
- oxidační stres * účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sulfhydrylové sloučeniny metabolismus MeSH
- výhonky rostlin metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia * MeSH
- kyselina askorbová MeSH
- látky znečišťující půdu MeSH
- nikl * MeSH
- reaktivní formy kyslíku MeSH
- sulfhydrylové sloučeniny MeSH
The structure and biochemical properties of protease inhibitors from the thyropin family are poorly understood in parasites and pathogens. Here, we introduce a novel family member, Ir-thyropin (IrThy), which is secreted in the saliva of Ixodes ricinus ticks, vectors of Lyme borreliosis and tick-borne encephalitis. The IrThy molecule consists of two consecutive thyroglobulin type-1 (Tg1) domains with an unusual disulfide pattern. Recombinant IrThy was found to inhibit human host-derived cathepsin proteases with a high specificity for cathepsins V, K, and L among a wide range of screened cathepsins exhibiting diverse endo- and exopeptidase activities. Both Tg1 domains displayed inhibitory activities, but with distinct specificity profiles. We determined the spatial structure of one of the Tg1 domains by solution NMR spectroscopy and described its reactive center to elucidate the unique inhibitory specificity. Furthermore, we found that the inhibitory potency of IrThy was modulated in a complex manner by various glycosaminoglycans from host tissues. IrThy was additionally regulated by pH and proteolytic degradation. This study provides a comprehensive structure-function characterization of IrThy-the first investigated thyropin of parasite origin-and suggests its potential role in host-parasite interactions at the tick bite site.
- Klíčová slova
- cathepsin, cysteine protease, parasite, protease inhibitor, protein structure, saliva, thyropin, tick,
- MeSH
- cystein MeSH
- glykosaminoglykany MeSH
- kathepsiny metabolismus MeSH
- klíště * metabolismus MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- sliny * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cystein MeSH
- glykosaminoglykany MeSH
- kathepsiny MeSH
We have previously identified a unique disulfide bond in the crystal structure of Arabidopsis cytosolic seryl-tRNA synthetase involving cysteines evolutionarily conserved in all green plants. Here, we discovered that both cysteines are important for protein stability, but with opposite effects, and that their microenvironment may promote disulfide bond formation in oxidizing conditions. The crystal structure of the C244S mutant exhibited higher rigidity and an extensive network of noncovalent interactions correlating with its higher thermal stability. The activity of the wild-type showed resistance to oxidation with H2 O2 , while the activities of cysteine-to-serine mutants were impaired, indicating that the disulfide link may enable the protein to function under oxidative stress conditions which can be beneficial for an efficient plant stress response.
- Klíčová slova
- aminoacyl-tRNA synthetase, cysteine reactivity, disulfide bond, hydrogen peroxide, oxidative stress, thermal stability,
- MeSH
- Arabidopsis * genetika metabolismus MeSH
- cystein genetika metabolismus MeSH
- disulfidy MeSH
- oxidace-redukce MeSH
- rostliny metabolismus MeSH
- serin-tRNA-ligasa * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cystein MeSH
- disulfidy MeSH
- serin-tRNA-ligasa * MeSH
