It has been documented that adaptation to hypoxia increases myocardial tolerance to ischemia-reperfusion (I/R) injury depending on the regimen of adaptation. Reactive oxygen species (ROS) formed during hypoxia play an important role in the induction of protective cardiac phenotype. On the other hand, the excess of ROS can contribute to tissue damage caused by I/R. Here we investigated the relationship between myocardial tolerance to I/R injury and transcription activity of major antioxidant genes, transcription factors, and oxidative stress in three different regimens of chronic hypoxia. Adult male Wistar rats were exposed to continuous normobaric hypoxia (FiO2 0.1) either continuously (CNH) or intermittently for 8 h/day (INH8) or 23 h/day (INH23) for 3 wk period. A control group was kept in room air. Myocardial infarct size was assessed in anesthetized open-chest animals subjected to 20 min coronary artery occlusion and 3 h reperfusion. Levels of mRNA transcripts and the ratio of reduced and oxidized glutathione (GSH/GSSG) were analyzed by real-time RT-PCR and by liquid chromatography, respectively. Whereas CNH as well as INH8 decreased infarct size, 1 h daily reoxygenation (INH23) abolished the cardioprotective effect and decreased GSH/GSSG ratio. The majority of mRNAs of antioxidant genes related to mitochondrial antioxidant defense (manganese superoxide dismutase, glutathione reductase, thioredoxin/thioredoxin reductase, and peroxiredoxin 2) were upregulated in both cardioprotective regimens (CNH, INH8). In contrast, INH23 increased only PRX5, which was not sufficient to induce the cardioprotective phenotype. Our results suggest that the increased mitochondrial antioxidant defense plays an important role in cardioprotection afforded by chronic hypoxia.
- Klíčová slova
- adaptation to hypoxia, antioxidant defense, cardioprotection, ischemia-reperfusion injury, oxidative stress,
- MeSH
- antioxidancia metabolismus MeSH
- chromatografie kapalinová MeSH
- glutathionreduktasa genetika MeSH
- hypoxie metabolismus MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus MeSH
- oxidační stres fyziologie MeSH
- peroxiredoxiny genetika MeSH
- reperfuzní poškození myokardu metabolismus MeSH
- superoxiddismutasa genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- glutathionreduktasa MeSH
- peroxiredoxiny MeSH
- superoxiddismutasa 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.
- Klíčová slova
- Hexavalent chromium, antioxidant defense, oxidative stress, selenoenzymes, trace elements,
- 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
- Názvy látek
- antioxidancia MeSH
- chrom MeSH
- dvojchroman draselný MeSH
- glutathion MeSH
- glutathionreduktasa MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
- měď MeSH
- stopové prvky MeSH
- thioredoxin-disulfidreduktasa MeSH
- železo MeSH
- zinek MeSH
In this work, we focused on the differences between bacterial cultures of E. coli obtained from swabs of infectious wounds of patients compared to laboratory E. coli. In addition, blocking of the protein responsible for the synthesis of glutathione (γ-glutamylcysteine synthase-GCL) using 10 mM buthionine sulfoximine was investigated. Each E. coli showed significant differences in resistance to antibiotics. According to the determined resistance, E. coli were divided into experimental groups based on a statistical evaluation of their properties as more resistant and more sensitive. These groups were also used for finding the differences in a dependence of the glutathione pathway on resistance to antibiotics. More sensitive E. coli showed the same kinetics of glutathione synthesis while blocking GCL (Km 0.1 µM), as compared to non-blocking. In addition, the most frequent mutations in genes of glutathione synthetase, glutathione peroxidase and glutathione reductase were observed in this group compared to laboratory E.coli. The group of "more resistant" E. coli exhibited differences in Km between 0.3 and 0.8 µM. The number of mutations compared to the laboratory E. coli was substantially lower compared to the other group.
- MeSH
- bakteriální léková rezistence účinky léků genetika MeSH
- buthionin sulfoximin farmakologie MeSH
- Escherichia coli účinky léků genetika MeSH
- glutathion genetika MeSH
- glutathionperoxidasa genetika MeSH
- glutathionreduktasa genetika MeSH
- glutathionsynthasa genetika MeSH
- kinetika MeSH
- lidé MeSH
- mutace účinky léků genetika MeSH
- signální transdukce účinky léků genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- buthionin sulfoximin MeSH
- glutathion MeSH
- glutathionperoxidasa MeSH
- glutathionreduktasa MeSH
- glutathionsynthasa MeSH
Hemoglobin Haná [β63(E7) His-Asn] is an unstable hemoglobin variant that was described in a Czech proband and her sister with Heinz body hemolytic anemia. The mother bearing the same mutation was asymptomatic; nevertheless, all three carriers had the same proportion of the mutant globin chains. Assessment of several erythrocyte antioxidant parameters revealed that both symptomatic children, unlike their asymptomatic mother, had significantly decreased glutathione reductase (GR) activity. Their GR activities were restorable in vitro by flavin adenine dinucleotide. The riboflavin supplementation improved their glutathione metabolism and ameliorated their hemolysis. Pre- and post-treatment assessment of the B(2) vitamers indicated suboptimal pre-treatment vitamin B(2) status in both children. This study provides evidence that partial GR deficiency may alter the clinical manifestation of an unstable hemoglobinopathy.
- MeSH
- dospělí MeSH
- flavinadenindinukleotid farmakologie MeSH
- glutathion metabolismus MeSH
- glutathionreduktasa genetika metabolismus MeSH
- Heinzova tělíska * MeSH
- hemoglobinopatie krev farmakoterapie genetika MeSH
- hemoglobiny abnormální genetika MeSH
- hemolytické anemie * krev farmakoterapie genetika MeSH
- lidé MeSH
- missense mutace * MeSH
- mladiství MeSH
- riboflavin aplikace a dávkování MeSH
- rodina * MeSH
- substituce aminokyselin MeSH
- vitamin B komplex aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- flavinadenindinukleotid MeSH
- glutathion MeSH
- glutathionreduktasa MeSH
- hemoglobiny abnormální MeSH
- riboflavin MeSH
- vitamin B komplex MeSH
A chromate-tolerant mutant chr1-663T bearing a stable one-gene mutation and its parental strain 6chr(+) were used to investigate the background of Cr(VI) tolerance in the fission yeast Schizosaccharomyces pombe. The mutant chr1-663T displayed a significantly decreased specific glutathione reductase (GR) activity coded by the pgr1 (+) gene compared with its parental strain. Transformants of the mutant chr1-663T with a nonintegrative pUR18N vector expressing the pgr1 (+) gene exhibited the same Cr(VI) sensitivity and specific GR activity as their parental strain, demonstrating the importance of the GR-NADPH system in Cr(VI) tolerance. Transformants, nevertheless, exhibited an increased intracellular peroxide concentration, a decreased Cr(VI)-reducing and HO*-producing ability, which suggested an unbalanced oxidoreduction state of cells and partial complementation of the GR function. No mutation was found in the sequences of the pgr1 (+) and the pap1 (+) (transcriptional regulatory gene of GR) genes of the Cr(VI)-tolerant mutant by sequence analysis.
- MeSH
- chromany metabolismus farmakologie MeSH
- down regulace * MeSH
- fungální léková rezistence MeSH
- glutathionreduktasa genetika metabolismus MeSH
- mutace * MeSH
- oxidace-redukce MeSH
- proteiny asociované s pankreatitidou MeSH
- Schizosaccharomyces pombe - proteiny genetika metabolismus MeSH
- Schizosaccharomyces účinky léků enzymologie genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chromany MeSH
- glutathionreduktasa MeSH
- proteiny asociované s pankreatitidou MeSH
- REG3A protein, human MeSH Prohlížeč
- Schizosaccharomyces pombe - proteiny MeSH
