Nejvíce citovaný článek - PubMed ID 19689357
Metallothioneins and cancer
Cadmium (Cd) is a heavy metal that occurs in all areas of the environment, including the food chain. In the body, it causes oxidative stress by producing free radicals that are harmful to the cells. Grape seed extract (GSE) contains a wide range of biologically active components that help to neutralize the adverse effects of free radicals. In this study, the effects of GSE prepared form semi-resistant grapevine cultivar Cerason, which is rich in phenolics, on biochemical markers of brown rats exposed to the effects of cadmium were monitored. GSE increased the plasma antioxidant activity and, in the kidneys and the liver, Cd content was significantly lowered by GSE co-administration. Accordingly, the increase in creatinine content and alanine aminotransferase activity and the decrease of catalase and superoxide dismutase activities caused by cadmium were slowed down by GSE co-administration. The results of this work reveal that grape seed extract offers a protective effect against the intake of heavy metals into the organism.
- Klíčová slova
- antioxidants, biochemical markers, cadmium, grape seed extract, protective effect, rattus norvegicus,
- MeSH
- alanintransaminasa krev MeSH
- antioxidancia analýza MeSH
- aspartátaminotransferasy krev MeSH
- biologické markery metabolismus MeSH
- extrakt ze semen vinné révy farmakologie MeSH
- fytonutrienty analýza MeSH
- játra účinky léků enzymologie metabolismus MeSH
- kadmium krev MeSH
- katalasa metabolismus MeSH
- kreatinin krev MeSH
- krysa rodu Rattus MeSH
- ledviny účinky léků metabolismus MeSH
- metalothionein metabolismus MeSH
- močovina krev MeSH
- potkani Wistar MeSH
- semena rostlinná chemie MeSH
- superoxiddismutasa metabolismus MeSH
- zdraví * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alanintransaminasa MeSH
- antioxidancia MeSH
- aspartátaminotransferasy MeSH
- biologické markery MeSH
- extrakt ze semen vinné révy MeSH
- fytonutrienty MeSH
- kadmium MeSH
- katalasa MeSH
- kreatinin MeSH
- metalothionein MeSH
- močovina MeSH
- superoxiddismutasa MeSH
Zinc ions are essential cofactors of a wide range of enzymes, transcription factors, and other regulatory proteins. Moreover, zinc is also involved in cellular signaling and enzymes inhibition. Zinc dysregulation, deficiency, over-supply, and imbalance in zinc ion transporters regulation are connected with various diseases including cancer. A zinc ion pool is maintained by two types of proteins: (i) zinc-binding proteins, which act as a buffer and intracellular donors of zinc and (ii) zinc transporters responsible for zinc fluxes into/from cells and organelles. The decreased serum zinc ion levels have been identified in patients suffering from various cancer diseases, including head and neck tumors and breast, prostate, liver, and lung cancer. On the contrary, increased zinc ion levels have been found in breast cancer and other malignant tissues. Zinc metalloproteomes of a majority of tumors including brain ones are still not yet fully understood. Current knowledge show that zinc ion levels and detection of certain zinc-containing proteins may be utilized for diagnostic and prognostic purposes. In addition, these proteins can also be promising therapeutic targets. The aim of the present work is an overview of the importance of zinc ions, zinc transporters, and zinc-containing proteins in brain tumors, which are, after leukemia, the second most common type of childhood cancer and the second leading cause of death in children after accidents.
- Klíčová slova
- Cancer, Childhood brain tumors, Metallothioneins, Zinc metalloenzymes, Zinc transporters,
- MeSH
- biologické modely MeSH
- cílená molekulární terapie MeSH
- dítě MeSH
- lidé MeSH
- nádorové proteiny metabolismus MeSH
- nádory mozku diagnóza metabolismus MeSH
- zinek metabolismus MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- nádorové proteiny MeSH
- zinek MeSH
BACKGROUND AND OBJECTIVES: Current studies give us inconsistent results regarding the association of neoplasms and zinc(II) serum and tissues concentrations. The results of to-date studies using meta-analysis are summarized in this paper. METHODS: Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL were searched. Articles were reviewed by two evaluators; quality was assessed by Newcastle-Ottawa scale; meta-analysis was performed including meta-regression and publication bias analysis. RESULTS: Analysis was performed on 114 case control, cohort and cross-sectional studies of 22737 participants. Decreased serum zinc level was found in patients with lung (effect size = -1.04), head and neck (effect size = -1.43), breast (effect size = -0.93), liver (effect size = -2.29), stomach (effect size = -1.59), and prostate (effect size = -1.36) cancers; elevation was not proven in any tumor. More specific zinc patterns are evident at tissue level, showing increase in breast cancer tissue (effect size = 1.80) and decrease in prostatic (effect size = -3.90), liver (effect size = -8.26), lung (effect size = -3.12), and thyroid cancer (effect size = -2.84). The rest of the included tumors brought ambiguous results, both in serum and tissue zinc levels across the studies. The association between zinc level and stage or grade of tumor has not been revealed by meta-regression. CONCLUSION: This study provides evidence on cancer-specific tissue zinc level alteration. Although serum zinc decrease was associated with most tumors mentioned herein, further--prospective--studies are needed.
- MeSH
- epitel patologie MeSH
- lidé MeSH
- nádory krev patologie MeSH
- statistické modely MeSH
- zinek krev MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Názvy látek
- zinek MeSH
Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03) and ovarian tumors (OR 7.83; 1.09-56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.
- MeSH
- databáze bibliografické MeSH
- imunohistochemie MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- metastázy nádorů MeSH
- nádorové biomarkery metabolismus MeSH
- nádory hlavy a krku diagnóza metabolismus patologie MeSH
- nádory jater diagnóza metabolismus patologie MeSH
- nádory vaječníků diagnóza metabolismus patologie MeSH
- odds ratio MeSH
- prognóza MeSH
- studie případů a kontrol MeSH
- stupeň nádoru MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Názvy látek
- metalothionein MeSH
- nádorové biomarkery MeSH
Metallothioneins (MT) are low molecular weight, cysteine-rich proteins maintaining metal ions homeostasis. They play a role in carcinogenesis and may also cause chemoresistance. The aim of the study was to explore the importance of MT serum levels in children suffering from malignant tumours. This prospective study involves examination of 865 samples from 172 patients with malignant tumours treated from 2008 to 2011 at University Hospital Motol. MT serum levels were determined using differential pulse voltammetry-Brdicka reaction. Mean MT level was 2.7 ± 0.5 μM. There was no statistically significant difference between MT levels in different tumours. We also did not find any correlation between MT levels and response to therapy or clinical stages. However, we found a positive correlation between MT levels and age (p = 0.009) and a negative correlation with absolute lymphocyte number (p = 0.001). The fact that patients who had early disease recurrence had lower MT levels during the treatment (complete remission 2.67 vs. recurring 2.34, p = 0.001) seems to be important for clinical practice. Accordingly we believe that there is benefit in further studies of serum MT levels in tumours.
- MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- metalothionein krev MeSH
- mladiství MeSH
- nádorové biomarkery krev MeSH
- nádory krev farmakoterapie MeSH
- předškolní dítě MeSH
- prognóza MeSH
- progrese nemoci MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- metalothionein MeSH
- nádorové biomarkery MeSH
Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Proteomics and metalloproteomics are rapidly developing interdisciplinary fields providing enormous amounts of data to be classified, evaluated and interpreted. Approaches offered by bioinformatics and also by biostatistical data analysis and treatment are therefore of extreme interest. Numerous methods are now available as commercial or open source tools for data processing and modelling ready to support the analysis of various datasets. The analysis of scientific data remains a big challenge, because each new task sets its specific requirements and constraints that call for the design of a targeted data pre-processing approach. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a mathematical approach for evaluating and classifying datasets obtained by electrochemical analysis of metallothionein in rat 9 tissues (brain, heart, kidney, eye, spleen, gonad, blood, liver and femoral muscle). Tissue extracts were heated and then analysed using the differential pulse voltammetry Brdicka reaction. The voltammograms were subsequently processed. Classification models were designed making separate use of two groups of attributes, namely attributes describing local extremes, and derived attributes resulting from the level=5 wavelet transform. CONCLUSIONS/SIGNIFICANCE: On the basis of our results, we were able to construct a decision tree that makes it possible to distinguish among electrochemical analysis data resulting from measurements of all the considered tissues. In other words, we found a way to classify an unknown rat tissue based on electrochemical analysis of the metallothionein in this tissue.
- MeSH
- elektrochemie metody MeSH
- interpretace statistických dat MeSH
- králíci MeSH
- krysa rodu Rattus MeSH
- metalothionein chemie MeSH
- potkani Wistar MeSH
- proteomika metody MeSH
- rozhodovací stromy MeSH
- statistické modely MeSH
- teoretické modely MeSH
- tkáňová distribuce * MeSH
- výpočetní biologie metody MeSH
- výzkumný projekt MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- metalothionein MeSH
Francisella tularensis is the causative agent of tularemia. It is an intracellular pathogen with the ability to survive within phagosomes and induce pyroptotic cell death. In this study, we attempted to prove whether oxidative imbalance plays a significant role in tularemia pathogenesis. In our experimental model, we subcutaneously infected female BALB/c mice (dose 10(5) CFU of F. tularensis LVS). Liver, spleen, and blood were collected from mice at regular intervals from days 1-15 after infection. The bacterial burden was assessed by a cultivation test. The burden was unchanging from the 2(nd) to 6(th) day after infection. The bacterial burden corresponded to the plasmatic level of IFN-γ, IL-6, and liver malondialdehyde. After the phase of acute bacteraemia and the innate immunity reaction, the levels of reduced glutathione and total low molecular weight antioxidants decreased significantly and the activity of caspase-3 increased in the liver. The level of reduced glutathione decreased to 25% of the original level, and the total level of low molecular weight antioxidants was less than 50% of the initial amount. The demonstrated effects of tularemia-induced pathology had a more extensive impact on the liver than on the spleen.
- MeSH
- antioxidancia analýza MeSH
- bakteriální nálož MeSH
- Francisella tularensis patogenita MeSH
- interferon gama krev MeSH
- interleukin-6 krev MeSH
- játra mikrobiologie MeSH
- krev mikrobiologie MeSH
- malondialdehyd analýza MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- oxidační stres * MeSH
- slezina mikrobiologie MeSH
- tularemie mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- interferon gama MeSH
- interleukin-6 MeSH
- malondialdehyd MeSH
Cadmium, as a hazardous pollutant commonly present in the living environment, represents an important risk to human health due to its undesirable effects (oxidative stress, changes in activities of many enzymes, interactions with biomolecules including DNA and RNA) and consequent potential risk, making its detection very important. New and unique technological and biotechnological approaches for solving this problems are intensely sought. In this study, we used the commonly occurring potential pathogenic microorganism Staphylococcus aureus for the determination of markers which could be used for sensing of cadmium(II) ions. We were focused on monitoring the effects of different cadmium(II) ion concentrations (0, 1.25, 2.5, 5, 10, 15, 25 and 50 μg mL(-1)) on the growth and energetic metabolism of Staphylococcus aureus. Highly significant changes have been detected in the metabolism of thiol compounds-specifically the protein metallothionein (0.79-26.82 mmol/mg of protein), the enzyme glutathione S-transferase (190-5,827 μmol/min/mg of protein), and sulfhydryl groups (9.6-274.3 μmol cysteine/mg of protein). The ratio of reduced and oxidized glutathione indicated marked oxidative stress. In addition, dramatic changes in urease activity, which is connected with resistance of bacteria, were determined. Further, the effects of cadmium(II) ions on the metabolic pathways of arginine, β-glucosidase, phosphatase, N-acetyl β-d-glucosamine, sucrose, trehalose, mannitol, maltose, lactose, fructose and total proteins were demonstrated. A metabolomic profile of Staphylococcus aureus under cadmium(II) ion treatment conditions was completed seeking data about the possibility of cadmium(II) ion accumulation in cells. The results demonstrate potential in the application of microorganisms as modern biosensor systems based on biological components.
- Klíčová slova
- Brdicka reaction, Staphylococcus aureus, biosensor, cadmium, electrochemistry, high performance liquid chromatography with electrochemical detection, metabolic activity, metabolome, microbiome, spectrophotometry, voltammetry,
- MeSH
- biosenzitivní techniky metody MeSH
- disacharidy metabolismus MeSH
- elektrochemické techniky MeSH
- fosfatasy metabolismus MeSH
- glutathion metabolismus MeSH
- glutathiondisulfid metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- hydrolasy metabolismus MeSH
- kadmium analýza metabolismus farmakologie MeSH
- látky znečišťující životní prostředí analýza metabolismus farmakologie MeSH
- metabolismus účinky léků MeSH
- metalothionein metabolismus MeSH
- monosacharidy metabolismus MeSH
- proliferace buněk účinky léků MeSH
- proteiny metabolismus MeSH
- Staphylococcus aureus cytologie účinky léků metabolismus MeSH
- sulfhydrylové sloučeniny metabolismus MeSH
- ureasa metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- arginine deiminase MeSH Prohlížeč
- disacharidy MeSH
- fosfatasy MeSH
- glutathion MeSH
- glutathiondisulfid MeSH
- glutathiontransferasa MeSH
- hydrolasy MeSH
- kadmium MeSH
- látky znečišťující životní prostředí MeSH
- metalothionein MeSH
- monosacharidy MeSH
- proteiny MeSH
- sulfhydrylové sloučeniny MeSH
- ureasa MeSH
The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.
- Klíčová slova
- anticancer therapy, metallothionein, platinum based anticancer drugs, resistance, retinoblastoma, tumor disease,
- MeSH
- antitumorózní látky * farmakokinetika farmakologie MeSH
- biologické modely MeSH
- cisplatina * farmakokinetika farmakologie MeSH
- karboplatina * farmakokinetika farmakologie MeSH
- králíci MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- nádorové buněčné linie MeSH
- neuroblastom * farmakoterapie metabolismus patologie MeSH
- retinoblastom * farmakoterapie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky * MeSH
- cisplatina * MeSH
- karboplatina * MeSH
- metalothionein MeSH