thiol-functionalization
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OBJECTIVES: The aim of this study was to investigate the associations between urinary arsenic, oxidative stress, assessed by thiol/disulphide homeostasis, and lung diseases in firefighters. METHODS: The study conducted among the municipality-based male firefighters (n = 100) who were admitted to occupational diseases clinic for periodic medical examination. The control group consisted of non-exposed male office workers (n = 50). Urinary arsenic levels, thiol/disulphide homeostasis parameters of participants were determined. Also, lung diseases were assessed by chest X-ray and pulmonary function tests. RESULTS: The mean age and work year did not differ in the study and control group. The median urinary arsenic concentration of firefighters was significantly higher than in the control group: 15.65 (2.5-246) μg/L and 3 (0.10-6) μg/L, respectively (p < 0.001). The parameters of pulmonary function tests (PFT) FVC (%), FEV1 (%), FEV1/FVC ratio and FEF 25-75 (%) were all significantly lower in firefighters compared to controls. A significant increase in mean serum disulphide concentration (17.10 ± 8.31 μmol/L vs. 7.48 ± 5.91) (Fig. 1) and disulphide/native thiol % ratio: 3.63 (0.53-11.43) vs. 1.51 (0.03-7.65) (p < 0.001) were found between exposed group and controls. The Spearman's correlation analysis revealed a positive correlation between urinary arsenic and disulphide (r = 0.422, p < 0.001), disulphide/native thiol % ratio (r = 0.409, p < 0.001). Nevertheless, urinary arsenic correlated negatively with all PFT parameters including FVC (%), FEV1 (%), FEV1/FVC and FEF 25-75 (%) (p < 0.001). CONCLUSION: We showed the arsenic-induced oxidative stress in firefighters with impairments of several lung functions determined by thiol/disulphide homeostasis using a novel method.
- MeSH
- arsen moč MeSH
- biologické markery krev moč MeSH
- časná diagnóza MeSH
- disulfidy krev MeSH
- dospělí MeSH
- hasiči * MeSH
- homeostáza MeSH
- lidé MeSH
- oxidační stres MeSH
- plicní nemoci krev diagnóza patofyziologie MeSH
- rentgendiagnostika hrudníku MeSH
- respirační funkční testy MeSH
- sulfhydrylové sloučeniny krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Turecko MeSH
One of the major obstacles that limits the use of magnetic nanoparticles in biomedical applications is their potential toxicity. In the present study, we evaluated the cytotoxic effects of thiol-functionalized silica-coated iron oxide (Fe3O4@SiO2-SH) nanoparticles using human lung epithelial cells A549. We investigated the effect of Fe3O4@SiO2-SH nanoparticles on the cell viability, proliferation, cell cycle distribution, adhesion, apoptosis, and the orientation of the cytoskeletal networks, as well as on expression of proteins involved in cell death, cell survival, and cell adhesion. We demonstrated that exposure of A549 cells to Fe3O4@SiO2-SH nanoparticles resulted in severe disruption of the actin microfilaments and microtubule cytoskeleton and reduced the size of focal adhesions. Furthermore, cell adhesion was significantly affected as well as the phosphorylation of focal adhesion kinase (FAK), extracellular-signal-regulated kinase (ERK), and p38. Our findings highlight the need for in-depth cytotoxic evaluation of nanoparticles supporting their safer use, especially in biomedical applications.
- MeSH
- buněčná adheze účinky léků MeSH
- buňky A549 MeSH
- cytoskelet účinky léků MeSH
- lidé MeSH
- magnetické nanočástice oxidů železa chemie toxicita MeSH
- oxid křemičitý chemie MeSH
- proliferace buněk účinky léků MeSH
- sulfhydrylové sloučeniny chemie MeSH
- železo chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Surface-modified gold multibranched nanoparticles (AuMs) were prepared by simple chemical reduction of gold chloride aqueous solution followed by in situ modification by using water-soluble arenediazonium tosylates with different functional organic groups. Chemical and morphological structures of the prepared nanoparticles were examined by using transmission electron and scanning electron microscopies. The covalent grafting of organic compounds was confirmed by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and Raman spectroscopy techniques. Covalent functionalization of nanoparticles significantly expands the range of their potential uses under physiological conditions, compared with traditional non-covalent or thiol-based approaches. The antibacterial effect of the surface-modified AuMs was evaluated by using Escherichia coli and Staphylococcus epidermidis bacteria under IR light illumination and without external triggering. Strong plasmon resonance on the AuMs cups leads to significant reduction of the light power needed kill bacteria under the mild conditions of continuous illumination. The effect of the surface-modified AuMs on the light-induced antibacterial activities was founded to be dependent on the grafted organic functional groups.
In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging.
Under normal conditions, the cellular redox status is maintained in a steady state by reduction and oxidation processes. These redox alterations in the cell are mainly sensed by protein thiol residues of cysteines thus regulating protein function. The imbalance in redox homeostasis may therefore regulate protein turnover either directly by redox modulating of transcription factors or indirectly by the degradation of damaged proteins due to oxidation. A new analytical method capable of simultaneously assessing cellular protein expression and cysteine oxidation would provide a valuable tool for the field of cysteine-targeted biology. Here, we show a workflow based on protein quantification using metabolic labeling and determination of cysteine oxidation using reporter ion quantification. We applied this approach to determine protein and redox changes in cells after 5-min, 60-min and 32-h exposure to H2O2, respectively. Based on the functional analysis of our data, we confirmed a biological relevance of this approach and its applicability for parallel mapping of cellular proteomes and redoxomes under diverse conditions. In addition, we revealed a specific pattern of redox changes in peroxiredoxins in a short time-interval cell exposure to H2O2. Overall, our present study offers an innovative, versatile experimental approach to the multifaceted assessment of cellular proteome and its redox status, with broad implications for biomedical research towards a better understanding of organismal physiology and diverse disease conditions.
- MeSH
- chromatografie kapalinová MeSH
- cystein metabolismus MeSH
- oxidace-redukce * MeSH
- oxidační stres MeSH
- peroxid vodíku metabolismus MeSH
- peroxiredoxiny metabolismus MeSH
- proteom * MeSH
- proteomika * metody MeSH
- tandemová hmotnostní spektrometrie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chelátory terapeutické užití MeSH
- daunomycin škodlivé účinky MeSH
- funkční vyšetření srdce MeSH
- králíci MeSH
- nemoci srdce chemicky indukované prevence a kontrola MeSH
- sulfhydrylové sloučeniny terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium.
- MeSH
- antioxidancia metabolismus MeSH
- časové faktory MeSH
- down regulace MeSH
- funkce levé komory srdeční MeSH
- katalasa metabolismus MeSH
- komorový tlak (srdce) MeSH
- kontrakce myokardu MeSH
- krysa rodu rattus MeSH
- myokard enzymologie MeSH
- oxidace-redukce MeSH
- perfuze MeSH
- reperfuzní poškození myokardu enzymologie patofyziologie prevence a kontrola MeSH
- sodíko-draslíková ATPasa metabolismus MeSH
- sulfhydrylové sloučeniny metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- syndrom omráčeného myokardu enzymologie patofyziologie prevence a kontrola MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme, a unique member of the peroxiredoxin family, with an important role in antioxidant defense. Moreover, it has also been linked with the biosynthesis of anti-inflammatory and anti-diabetic lipids called fatty acid esters of hydroxy fatty acids (FAHFAs) and many diseases, including cancer, inflammation, and metabolic disorders. Here, we performed metabolomic and lipidomic profiling of subcutaneous adipose tissue from mouse models with genetically modified Prdx6. Deletion of Prdx6 resulted in reduced levels of FAHFAs containing 13-hydroxylinoleic acid (13-HLA). Mutation of Prdx6 C47S impaired the glutathione peroxidase activity and reduced FAHFA levels, while D140A mutation, responsible for phospholipase A2 activity, showed only minor effects. Targeted analysis of oxidized phospholipids and triacylglycerols in adipocytes highlighted a correlation between FAHFA and hydroxy fatty acid production by Prdx6 or glutathione peroxidase 4. FAHFA regioisomer abundance was negatively affected by the Prdx6 deletion, and this effect was more pronounced in longer and more unsaturated FAHFAs. The predicted protein model of Prdx6 suggested that the monomer-dimer transition mechanism might be involved in the repair of longer-chain peroxidized phospholipids bound over two monomers and that the role of Prdx6 in FAHFA synthesis might be restricted to branching positions further from carbon 9. In conclusion, our work linked the peroxidase activity of Prdx6 with the levels of FAHFAs in adipose tissue.
- MeSH
- antioxidancia MeSH
- fosfolipidy MeSH
- mastné kyseliny MeSH
- metabolomika * MeSH
- myši MeSH
- peroxiredoxin VI * genetika MeSH
- peroxiredoxiny MeSH
- tukové buňky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Thieme foundations of organic chemistry series
[1st ed.] xv, 260 s. : il.