Microorganisms produce volatile compounds (VCs) that promote plant growth and photosynthesis through complex mechanisms involving cytokinin (CK) and abscisic acid (ABA). We hypothesized that plants' responses to microbial VCs involve posttranslational modifications of the thiol redox proteome through action of plastidial NADPH-dependent thioredoxin reductase C (NTRC), which regulates chloroplast redox status via its functional relationship with 2-Cys peroxiredoxins. To test this hypothesis, we analysed developmental, metabolic, hormonal, genetic, and redox proteomic responses of wild-type (WT) plants and a NTRC knockout mutant (ntrc) to VCs emitted by the phytopathogen Alternaria alternata. Fungal VC-promoted growth, changes in root architecture, shifts in expression of VC-responsive CK- and ABA-regulated genes, and increases in photosynthetic capacity were substantially weaker in ntrc plants than in WT plants. As in WT plants, fungal VCs strongly promoted growth, chlorophyll accumulation, and photosynthesis in ntrc-Δ2cp plants with reduced 2-Cys peroxiredoxin expression. OxiTRAQ-based quantitative and site-specific redox proteomic analyses revealed that VCs promote global reduction of the thiol redox proteome (especially of photosynthesis-related proteins) of WT leaves but its oxidation in ntrc leaves. Our findings show that NTRC is an important mediator of plant responses to microbial VCs through mechanisms involving global thiol redox proteome changes that affect photosynthesis.

• MeSH
• Alternaria * MeSH
• Arabidopsis účinky léků   metabolismus   MeSH
• cytokininy metabolismus   MeSH
• fotosyntéza účinky léků   MeSH
• kyselina abscisová metabolismus   MeSH
• posttranslační úpravy proteinů účinky léků   MeSH
• proteiny huseníčku metabolismus   MeSH
• proteom MeSH
• těkavé organické sloučeniny farmakologie   MeSH
• thioredoxin-disulfidreduktasa metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.

• MeSH
• adenom krev   genetika   MeSH
• genetické markery MeSH
• glutathionperoxidasa genetika   metabolismus   MeSH
• kohortové studie MeSH
• kolorektální nádory krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• regulace genové exprese MeSH
• selen krev   MeSH
• selenoprotein P genetika   metabolismus   MeSH
• selenoproteiny genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thioredoxin-disulfidreduktasa genetika   metabolismus   MeSH
• thioredoxinreduktasa 1 genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Irsko MeSH

Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure-activity-relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2-furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4-ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion.

• MeSH
• anisoly chemie   MeSH
• buňky HT-29 MeSH
• fosfiny chemie   MeSH
• kationty jednomocné MeSH
• komplexní sloučeniny chemická syntéza   farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• mitogenem aktivovaná proteinkinasa 1 genetika   metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 genetika   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádory plic farmakoterapie   patologie   MeSH
• organické sloučeniny zlata chemická syntéza   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• proteiny tepelného šoku HSP27 genetika   metabolismus   MeSH
• protinádorové látky chemická syntéza   farmakologie   MeSH
• thioredoxin-disulfidreduktasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zlato chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of diabetes and its complications. The aim of this study was to examine the possible association between seven single nucleotide polymorphisms (SNPs) of the Trx2/TXNIP and TrxR2 genes encoding proteins involved in the thioredoxin antioxidant defence system and the risk of diabetic retinopthy (DR). DESIGN: Cross-sectional case-control study. PARTICIPANTS: A total of 802 Slovenian patients with Type 2 diabetes mellitus; 277 patients with DR and 525 with no DR were enrolled. METHODS: Patients genotypes of the SNPs; including rs8140110, rs7211, rs7212, rs4755, rs1548357, rs4485648 and rs5748469 were determined by the competitive allele specific PCR method. MAIN OUTCOME MEASURES: Each genotype of examined SNPs was regressed in a logistic model, assuming the co-dominant, dominant and the recessive models of inheritance with covariates of duration of diabetes, HbA1c, insulin therapy, total cholesterol and LDL cholesterol levels. RESULTS: In the present study, for the first time we identified an association between the rs4485648 polymorphism of the TrxR2 gene and DR in Caucasians with Type 2 DM. The estimated ORs of adjusted logistic regression models were found to be as follows: 4.4 for CT heterozygotes, 4.3 for TT homozygotes (co-dominant genetic model) and 4.4 for CT+TT genotypes (dominant genetic model). CONCLUSIONS: In our case-control study we were not able to demonstrate any association between rs8140110, rs7211, rs7212, rs4755, rs1548357, and rs5748469 and DR, however, our findings provide evidence that the rs4485648 polymorphism of the TrxR2 gene might exert an independent effect on the development of DR.

• MeSH
• diabetes mellitus 2. typu komplikace   genetika   MeSH
• diabetická retinopatie genetika   MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické sítě a dráhy genetika   MeSH
• mitochondriální proteiny genetika   MeSH
• mitochondrie genetika   metabolismus   MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thioredoxinreduktasa 2 genetika   MeSH
• thioredoxiny genetika   metabolismus   MeSH
• transportní proteiny genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin--conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin.

• MeSH
• aldehyddehydrogenasa genetika   metabolismus   MeSH
• aldehydy krev   MeSH
• apoferritiny aplikace a dávkování   chemie   toxicita   MeSH
• biologické markery krev   MeSH
• down regulace MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   chemie   toxicita   MeSH
• farmaceutická chemie MeSH
• játra účinky léků   enzymologie   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• polyethylenglykoly aplikace a dávkování   chemie   toxicita   MeSH
• potkani Wistar MeSH
• protinádorová antibiotika aplikace a dávkování   chemie   toxicita   MeSH
• regulace genové exprese enzymů MeSH
• thioredoxinreduktasa 2 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Occupational exposure to hexavalent chromium (Cr(VI)) compounds is of concern in many Cr-related industries and their surrounding environment. Cr(VI) is a proven toxin and carcinogen. The Cr(VI) compounds are easily absorbed, can diffuse across cell membranes, and have strong oxidative potential. Despite intensive studies of Cr(VI) pro-oxidative effects, limited data exist on the influence of Cr(VI) on selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx)-important components of antioxidant defense system. This study investigates the effect of Cr(VI) exposure on antioxidant defense status, with focus on these selenoenzymes, and on trace element homeostasis in an acute experiment in rat. Male Wistar rats (130-140g) were assigned to two groups of 8 animals: I. control; and II. Cr(VI) treated. The animals in Cr(VI) group were administered a single dose of K2Cr2O7 (20 mg /kg, intraperitoneally (ip)). The control group received saline solution. After 24 h, the animals were sacrificed and the liver and kidneys were examined for lipid peroxidation (LP; thiobarbituric acid reactive substances (TBARS) concentration), the level of reduced glutathione (GSH) and the activities of GPx-1, TrxR-1, and glutathione reductase (GR). Samples of tissues were also used to estimate Cr accumulation and alterations in zinc, copper, and iron levels. The acute Cr(VI) exposure caused an increase in both hepatic and renal LP (by 70%, p < 0.01 and by 15%, p < 0.05, respectively), increased hepatic GSH level and GPx-1 activity, and decreased renal GPx-1 activity. The activity of GR was not changed. A significant inhibitory effect of Cr(VI) was found on TrxR-1 activity in both the liver and the kidneys. The ability of Cr(VI) to cause TrxR inhibition could contribute to its cytotoxic effects. Further investigation of oxidative responses in different in vivo models may enable the development of strategies to protect against Cr(VI) oxidative damage.

• MeSH
• antioxidancia metabolismus   MeSH
• chrom toxicita   MeSH
• dvojchroman draselný toxicita   MeSH
• glutathion metabolismus   MeSH
• glutathionreduktasa genetika   metabolismus   MeSH
• homeostáza účinky léků   MeSH
• játra účinky léků   metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• krysa rodu rattus MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• ledviny účinky léků   metabolismus   MeSH
• měď metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• stopové prvky farmakologie   MeSH
• thioredoxin-disulfidreduktasa antagonisté a inhibitory   metabolismus   MeSH
• železo metabolismus   MeSH
• zinek metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this study, oxidative stress-related parameters and As retention were examined in liver and kidneys of male Wistar rats exposed to arsenic trioxide, sodium arsenite (iAsIII), sodium arsenate (iAsV), and dimethylarsinic acid (DMAsV) at a single ip dose of 3.8 mgAs/kgbw, at 24h post-exposure. In liver, lipid peroxidation increased in iAsIII-exposed rats, glutathione peroxidase activity decreased in inorganic arsenic (iAs)-exposed rats, and catalase and thioredoxin reductase activities decreased significantly in all As-exposed groups. Both As(III) and As(V) exposure elevated GSH level with no effect on glutathione reductase activity. In kidneys, catalase activity decreased significantly in iAs-exposed, rats; GSH level, glutathione reductase and thioredoxin reductase activity decreased in DMAsV-treated, rats. The tissue As retention was higher in kidneys compared to liver and was also higher in As(III)-exposed compared to As(V)-exposed rats. The results demonstrate similar potency of inorganic As(III) and As(V) compounds to inhibit/induce antioxidant defense system, with liver being more vulnerable to acute As(III)- and As(V)-induced oxidative stress.

• MeSH
• antioxidancia metabolismus   MeSH
• arsen analýza   MeSH
• arsenikové přípravky * MeSH
• glutathion metabolismus   MeSH
• indikátory a reagencie MeSH
• játra účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• ledviny účinky léků   metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• selen farmakologie   MeSH
• thioredoxin-disulfidreduktasa metabolismus   MeSH
• thioredoxiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Odstranění deficitu selenu může mít za následek zlepšení zdravotního stavu mechanismy zvýšené antioxidační kapacity selenoenzymů a zlepšení imunity, které by se projevily zejména snížením infekcí a zánětů, ale i dalších oxidativních nemocí. Nedostatkem selenu trpí především senioři, kteří jsou současně nejvíce postiženi uvedenými chorobami (bakteriální a virové infekce, arthróza, kardiovaskulární a neurodegenerativní onemocnění, malignity). Projekt navrhuje 4leté sledování změn zdravotního stavu a vybraných fyziologických a biochemických parametrů 150ti seniorů s optimalizovaným stavem Se a porovnání se stejnou skupinou seniorů s placebem. Výsledky studie by mohly přinést po uvedení do praxe zlepšení kvality života starších věkových kategorií zlepšenímzdravotního, fyzického i psychického stavu, vést k prodloužení průměrného lidského života v ČR a k ušetření značných finančních prostředků; Elimination of Se deficit might have health consequences in decrease of infections, chronic inflammations and various oxidative diseased by the mechanisms of increased antioxidative capacities of selenoenzymes and improved immune response. Especially seniors suffer from Se deficiency and just people in old age the most often fall ill with this type of disease (bacterial and viral inflammations, arthrosis, cardiovascular and neurodegenerative diseases). This project suggests 4 years' monitoring of the health status and changes of selected physiological and biochemical parameters of 150 old persons with optimalized Se status and comparison of the results with health status of 150 seniors with placebo. Application of results might increase life quality ofelderly by improving their health as well as physical and mental status, extend lifespan in the CR, and spare money by prevention of serious diseases and their more effective treatment.

• MeSH
• glutathionperoxidasa MeSH
• hormony štítné žlázy MeSH
• imunita MeSH
• lipidy MeSH
• selen nedostatek   terapeutické užití   MeSH
• selenocystein MeSH
• senioři MeSH
• stopové prvky MeSH
• thioredoxinreduktasa 1 MeSH
• zdravotní stav MeSH
• Check Tag
• senioři MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• alergologie a imunologie
• geriatrie
• biochemie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Iron is an essential element which, under certain conditions, can have prooxidant and cancerogenic effects. The effect of iron and iron chelators on the activity of selenoenzymes has been studied. Acute experiments in male Wistar rats demonstrated the prooxidant effect of iron on the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx). These enzymes represent an important part of the antioxidant defense system. Deferiprone (L1) has been shown to abolish the stimulating effect of iron on lipid peroxidation and reduced glutathione (GSH) levels, and also to inhibit the influence of iron on the activity of TrxR and GPx. Similarly, the flavonoid quercetin abolished the influence of iron on the activity of TrxR. The activity of both selenoenzymes has also been shown to be stimulated using L1, naringin (NAR), quercetin (QUE) and myricetin (MYR) in the absence of iron. Further studies including the combination of synthetic and natural compounds (e.g., flavonoids) are being considered for their possible development and clinical use in antioxidant therapies.

• MeSH
• antioxidancia metabolismus   MeSH
• chelátory železa chemie   farmakologie   MeSH
• flavanony chemie   farmakologie   MeSH
• flavonoidy chemie   farmakologie   MeSH
• glutathionperoxidasa metabolismus   MeSH
• játra účinky léků   enzymologie   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• pyridony chemie   farmakologie   MeSH
• quercetin chemie   farmakologie   MeSH
• thioredoxin-disulfidreduktasa metabolismus   MeSH
• železo antagonisté a inhibitory   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Selenium is a trace element performing important biological functions in many organisms including humans. It usually affects organisms in a strictly dosage-dependent manner being essential at low and toxic at higher concentrations. The impact of selenium on mammalian and land plant cells has been quite extensively studied. Information about algal cells is rare despite of the fact that they could produce selenium enriched biomass for biotechnology purposes. RESULTS: We studied the impact of selenium compounds on the green chlorococcal alga Scenedesmus quadricauda. Both the dose and chemical forms of Se were critical factors in the cellular response. Se toxicity increased in cultures grown under sulfur deficient conditions. We selected three strains of Scenedesmus quadricauda specifically resistant to high concentrations of inorganic selenium added as selenite (Na2SeO3) - strain SeIV, selenate (Na2SeO4) - strain SeVI or both - strain SeIV+VI. The total amount of Se and selenomethionine in biomass increased with increasing concentration of Se in the culturing media. The selenomethionine made up 30-40% of the total Se in biomass. In both the wild type and Se-resistant strains, the activity of thioredoxin reductase, increased rapidly in the presence of the form of selenium for which the given algal strain was not resistant. CONCLUSION: The selenium effect on the green alga Scenedesmus quadricauda was not only dose dependent, but the chemical form of the element was also crucial. With sulfur deficiency, the selenium toxicity increases, indicating interference of Se with sulfur metabolism. The amount of selenium and SeMet in algal biomass was dependent on both the type of compound and its dose. The activity of thioredoxin reductase was affected by selenium treatment in dose-dependent and toxic-dependent manner. The findings implied that the increase in TR activity in algal cells was a stress response to selenium cytotoxicity. Our study provides a new insight into the impact of selenium on green algae, especially with regard to its toxicity and bioaccumulation.

• MeSH
• biomasa MeSH
• Scenedesmus metabolismus   růst a vývoj   účinky léků   MeSH
• seleničitan sodný metabolismus   toxicita   MeSH
• selenomethionin metabolismus   MeSH
• síra metabolismus   MeSH
• sloučeniny selenu toxicita   MeSH
• thioredoxin-disulfidreduktasa metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Publikační typ
• práce podpořená grantem MeSH