Metallothioneins (MTs), low molecular mass cysteine-rich proteins, which are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions are widely studied due to their functions in detoxification of metals, scavenging free radicals and cells protection against the oxidative stress. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic processes and carcinogenesis. The most extensive area is MTs expression for oncological applications, where the information about gene patterns is helpful for the identification biological function, resistance to drugs and creating the correct chemotherapy. In other medical applications the effect of oxidative stress to cell lines exposed to heavy metals and hydrogen peroxide is studied as well as influence of drugs and cytokines on MTs expression and MTs expression in the adipose tissue. The precise detection of low metallothionein concentrations and its isoforms is necessary to understand the connection between quantity and isoforms of MTs to size, localization and type of cancer. This information is necessary for well-timed therapy and increase the chance to survival. Microarray chips appear as good possibility for finding all information about expression of MTs genes and isoforms not only in cancer, but also in other diseases, especially diabetes, obesity, cardiovascular diseases, ageing, osteoporosis, psychiatric disorders and as the effects of toxic drugs and pollutants, which is discussed in this review.
The present study suggests and describes the application of a delivery system for antisense oligonucleotides against mRNA encoding estrogen receptor proteins α and β. The delivery system is composed of a cationic liposome envelope containing 17β-estradiol (E2) in its structure. Cationic liposomes protect cargo against the extracellular matrix, and E2 can increase its shuttling efficiency into cells. Using MCF-7 cells derived from estrogen receptor-positive ductal carcinoma, treatment with liposomes against ERα was found to decrease MCF-7 proliferation, and importantly the application of both the antisense against ERα and β exhibited an antiproliferative effect expressed as cell viability. Using qRT-PCR, it was shown that MT1A, NF-κB1 and K-ras genes, but not TFF1, were downregulated using E2-based liposomes (evaluated at P=0.05). Further indicators of oxidative stress were employed to assess the effect on treatment efficiency. Glutathione (GSH/GSSG redox ratio), metallothionein (MT) and malondialdehyde (MDA) confirmed a positive effect of antisense therapy resulting in their decreased levels in the MCF-7 cells. Based on these data, we suggest that E2-based liposomes offer sufficient transfer efficiency and moreover, due to the effect on NF-κB1, MT and GSH, tumor cells can be chemosensitized to increase treatment effectiveness.
- MeSH
- antitumorózní látky chemie MeSH
- estradiol metabolismus MeSH
- genetická terapie metody MeSH
- glutathion chemie MeSH
- koncentrace vodíkových iontů MeSH
- kyslík chemie MeSH
- lidé MeSH
- liposomy chemie MeSH
- malondialdehyd chemie MeSH
- metalothionein chemie MeSH
- MFC-7 buňky MeSH
- mikroskopie fázově kontrastní MeSH
- nádorové buněčné linie MeSH
- nádory prsu metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres MeSH
- proliferace buněk MeSH
- receptory pro estrogeny metabolismus MeSH
- regulace genové exprese MeSH
- systémy cílené aplikace léků * MeSH
- viabilita buněk MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this study, we focused on the effect of heavy metal ions in resistant strains of gram-positive bacteria Staphylococcus aureus using biochemical methods and mass spectrometry. Five nitrate solutions of heavy metals (Ag(+), Cu(2+), Cd(2+), Zn(2+) and Pb(2+)) were used to create S. aureus resistant strains. Biochemical changes of resistant strains in comparison with the non-resistant control strain of S. aureus were observed by microbiological (measuring - growth curves and inhibition zones) and spectrophotometric methods (antioxidant activity and alaninaminotransferase, aspartateaminotransferase, alkaline phosphatase, γ-glutamyltransferase activities). Mass spectrometry was employed for the qualitative analysis of the samples (changes in S. aureus protein composition) and for the identification of the strains database MALDI Biotyper was employed. Alterations, in terms of biochemical properties and protein composition, were observed in resistant strains compared to non-resistant control strain. Our results describe the possible option for the analysis of S. aureus resistant strains and may thus serve as a support for monitoring of changes in genetic information caused by the forming of resistance to heavy metals.
- MeSH
- hmotnostní spektrometrie MeSH
- ionty metabolismus farmakologie MeSH
- kovy metabolismus farmakologie MeSH
- metabolom MeSH
- metabolomika metody MeSH
- metalothionein chemie metabolismus MeSH
- mikrobiální viabilita účinky léků MeSH
- RNA ribozomální genetika MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- Staphylococcus aureus účinky léků genetika růst a vývoj metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Interaction between semiconductor nanocrystals, cadmium telluride quantum dots (CdTe QDs) capped with mercaptosuccinic acid (MSA) and metallothionein (MT) was investigated. MSA-capped CdTe QDs were synthesized in aqueous solution. Mixture of MT and MSA-capped CdTe QDs has been investigated by various analytical methods as follows: tris-tricine gel electrophoresis, fluorescence evaluation and electrochemical detection of catalysed hydrogen evolution. The obtained results demonstrate that MSA-capped CdTe QDs and MT do not create firmly bound stabile complex. However, weak electrostatic interactions contribute to the interaction of MT with MSA-capped CdTeQDs. It can be concluded that QDs size influences the QDs and MT interaction. The smallest QDs had the highest affinity to MT and vice versa.
- MeSH
- elektrochemické techniky MeSH
- fluorescenční spektrometrie MeSH
- králíci MeSH
- kvantové tečky * MeSH
- metalothionein chemie MeSH
- molekulární struktura MeSH
- nanočástice * MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
There is an arising and concerning issue in the field of bacterial resistance, which is confirmed by the number of deaths associated with drug-resistant bacterial infections. The aim of this study was to compare the effects of antibiotics on Staphylococcus aureus non-resistant strain and strains resistant to cadmium or lead ions. Metal resistant strains were created by the gradual addition of 2 mM solution of metal ions (cadmium or lead) to the S. aureus culture. An increasing antimicrobial effect of ampicillin, streptomycin, penicillin and tetracycline (0, 10, 25, 50, 75, 150, 225 and 300 µM) on the resistant strains was observed using a method of growth curves. A significant growth inhibition (compared to control) of cadmium resistant cells was observed in the presence of all the four different antibiotics. On the other hand, the addition of streptomycin and ampicillin did not inhibit the growth of lead resistant strain. Other antibiotics were still toxic to the bacterial cells. Significant differences in the morphology of cell walls were indicated by changes in the cell shape. Our data show that the presence of metal ions in the urban environment may contribute to the development of bacterial strain resistance to other substances including antibiotics, which would have an impact on public health.
- MeSH
- dobročinnost MeSH
- finanční podpora výzkumu jako téma MeSH
- nádory MeSH
- Publikační typ
- zprávy MeSH
In this study, the basic facts about the relationship between metallothionein and metals are summarized, determining the affinity of the interaction of metallothionein with different metals and the importance of this interaction for the functioning of organisms. In two described experiments there was presented significance of metallothionein determination in organism exposure to heavy metals.
