AIMS: Increased plasma soluble endoglin concentrations (sEng) are frequently detected in metabolic disorders accompanied with hypercholesterolemia in serum, but effect of sEng on the cholesterol biochemistry is unknown. Cholesterol and bile acids (BA) are important products of liver metabolism with numerous functions within the organism. Turnover of these substances requires precise regulation due to potential toxicities during their cumulation. In this study, we hypothesized that high sEng levels affect cholesterol homeostasis and BA turnover in mice liver. MAIN METHODS: Nine-month-old transgenic male mice overexpressing human sEng and wild-type mice underwent plasma, bile, stool, and organ samples analysis by analytical, qRT-PCT and Western blot methods. KEY FINDINGS: sEng mice demonstrated decreased plasma total and LDL cholesterol concentrations due to upregulation of hepatic Sr-b1 and Ldlr receptors, increased liver cholesterol content, and increased Abcg8-mediated cholesterol efflux into bile. sEng also increased conversion of cholesterol into bile acids (BA) via upregulation of Cyp7a1 and increased Mdr1 expression. Plasma concentrations of BA were increased in sEng mice due to their enhanced reabsorption via ileum. Increased hepatic disposition of BA led to their increased biliary excretion coupled with choleretic activity. SIGNIFICANCE: For the first time, we have shown that high sEng plasma levels affect cholesterol and BA homeostasis on the basis of complex liver and intestinal effects. The significance of these findings for pathophysiology of diseases associated with increased sEng concentrations remains to be elucidated in prospective studies.

• MeSH
• cholesterol krev   metabolismus   MeSH
• endoglin krev   fyziologie   MeSH
• feces MeSH
• homeostáza * MeSH
• játra metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• oxidační stres MeSH
• přenašeče organických aniontů závislé na sodíku metabolismus   MeSH
• protein SREBP2 metabolismus   MeSH
• receptory LDL metabolismus   MeSH
• symportéry metabolismus   MeSH
• upregulace MeSH
• zánět krev   MeSH
• žlučové kyseliny a soli krev   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Genomics methodologies have significantly improved elucidation of Mendelian disorders. The combination with high-throughput functional-omics technologies potentiates the identification and confirmation of causative genetic variants, especially in singleton families of recessive inheritance. In a cohort of 99 individuals with abnormal Golgi glycosylation, 47 of which being unsolved, glycomics profiling was performed of total plasma glycoproteins. Combination with whole-exome sequencing in 31 cases revealed a known genetic defect in 15 individuals. To identify additional genetic factors, hierarchical clustering of the plasma glycomics data was done, which indicated a subgroup of four patients that shared a unique glycomics signature of hybrid type N-glycans. In two siblings, compound heterozygous mutations were found in SLC10A7, a gene of unknown function in human. These included a missense mutation that disrupted transmembrane domain 4 and a mutation in a splice acceptor site resulting in skipping of exon 9. The two other individuals showed a complete loss of SLC10A7 mRNA. The patients' phenotype consisted of amelogenesis imperfecta, skeletal dysplasia, and decreased bone mineral density compatible with osteoporosis. The patients' phenotype was mirrored in SLC10A7 deficient zebrafish. Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization. Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane. In contrast to yeast, human SLC10A7 localized to the Golgi. Our combined data indicate an important role for SLC10A7 in bone mineralization and transport of glycoproteins to the extracellular matrix.

• MeSH
• dánio pruhované genetika   růst a vývoj   metabolismus   MeSH
• dospělí MeSH
• exom MeSH
• fenotyp MeSH
• fibroblasty metabolismus   patologie   MeSH
• fyziologická kalcifikace * MeSH
• genomika * MeSH
• glykomika * MeSH
• glykopeptidasa nedostatek   MeSH
• glykosylace MeSH
• Golgiho aparát metabolismus   patologie   MeSH
• kohortové studie MeSH
• kojenec MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace * MeSH
• přenašeče organických aniontů závislé na sodíku genetika   metabolismus   MeSH
• rodokmen MeSH
• symportéry genetika   metabolismus   MeSH
• transport proteinů MeSH
• vrozené poruchy glykosylace komplikace   MeSH
• vývojové onemocnění kostí etiologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dekkera bruxellensis is important for lambic beer fermentation but is considered a spoilage yeast in wine fermentation. We compared two D. bruxellensis strains isolated from wine and found that they differ in some basic properties, including osmotolerance. The genomes of both strains contain two highly similar copies of genes encoding putative glycerol-proton symporters from the STL family that are important for yeast osmotolerance. Cloning of the two DbSTL genes and their expression in suitable osmosensitive Saccharomyces cerevisiae mutants revealed that both identified genes encode functional glycerol uptake systems, but only DbStl2 has the capacity to improve the osmotolerance of S. cerevisiae cells.

• MeSH
• Dekkera genetika   izolace a purifikace   metabolismus   fyziologie   MeSH
• druhová specificita MeSH
• fungální proteiny genetika   metabolismus   MeSH
• genom bakteriální genetika   MeSH
• glycerol metabolismus   MeSH
• osmoregulace genetika   MeSH
• protony MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   MeSH
• symportéry genetika   metabolismus   MeSH
• testy genetické komplementace MeSH
• víno mikrobiologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

In the central nervous system (CNS), monocarboxylate transporter 1 (MCT1) is expressed in astrocytes and endothelial cells but also in oligodendroglia. Oligodendroglia support neurons and axons through lactate transportation by MCT1. Limited information is available on the MCT1 expression changes in candidate cells in the developing rat brain, especially in corpus callosum which is the most vulnerable area in demyelinating diseases. In the present study, we investigated the expression pattern of MCT1 during postnatal development in the rat corpus callosum using immunofluorescene staining, Western blotting analysis and RT-PCR. We reported that MCT1 gene and protein were consistently expressed in the rat corpus callosum from birth to adult. MCT1/CNPase and MCT1/GFAP immunofluorescence staining demonstrated that most of MCT1 positive cells were co-labeled with cyclic nucleotide 3´ phosphodiesterase (CNPase) in rat corpus callosum from P7 to adult, whereas MCT1(+)/GFAP(+) cells preserve the dominate position before P7. Moreover, there were significant associations between the expression of MCT1 protein and the expression of myelin basic protein (MBP) (correlation coefficient: r=0.962, P=0.009) from P7 to adult. Similarly, the MCT1 mRNA expression was also significantly associated with MBP mRNA expression (r=0.976, P=0.005). Our results are proposing that in the developing brain white matter, MCT1 is predominately expressed in oligodendrocyte though it mainly expressed in astrocyte in early postnatal, which indicate that MCT1 may involve in the oligodendrocyte development and myelination.

• MeSH
• bílá hmota metabolismus   MeSH
• corpus callosum metabolismus   MeSH
• krysa rodu rattus MeSH
• novorozená zvířata MeSH
• orgánová specificita MeSH
• potkani Sprague-Dawley MeSH
• přenašeče monokarboxylových kyselin metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• stárnutí metabolismus   MeSH
• symportéry metabolismus   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tuberous sclerosis complex (TSC) is a rare multi-system genetic disease characterized by several neurological disorders, the most common of which is the refractory epilepsy caused by highly epileptogenic cortical lesions. Previous studies suggest an alteration of GABAergic and glutamatergic transmission in TSC brain indicating an unbalance of excitation/inhibition that can explain, at least in part, the high incidence of epilepsy in these patients. Here we investigate whether TSC cortical tissues could retain GABAA and AMPA receptors at early stages of human brain development thus contributing to the generation and recurrence of seizures. Given the limited availability of pediatric human brain specimens, we used the microtransplantation method of injecting Xenopus oocytes with membranes from TSC cortical tubers and control brain tissues. Moreover, qPCR was performed to investigate the expression of GABAA and AMPA receptor subunits (GABAA α1-5, β3, γ2, δ; GluA1, GluA2) and cation chloride co-transporters NKCC1 and KCC2. The evaluation of nine human cortical brain samples, from 15 gestation weeks to 15years old, showed a progressive shift towards more hyperpolarized GABAA reversal potential (EGABA). This shift was associated with a differential expression of the chloride cotransporters NKCC1 and KCC2. Furthermore, the GluA1/GluA2 mRNA ratio of expression paralleled the development process. On the contrary, in oocytes micro-transplanted with epileptic TSC tuber tissue from seven patients, neither the GABAA reversal potential nor the GluA1/GluA2 expression showed similar developmental changes. Our data indicate for the first time, that in the same cohort of TSC patients, the pattern of both GABAAR and GluA1/GluA2 functions retains features that are typical of an immature brain. These observations support the potential contribution of altered receptor function to the epileptic disorder of TSC and may suggest novel therapeutic approaches. Furthermore, our findings strengthen the novel hypothesis that other developmental brain diseases can share the same hallmarks of immaturity leading to intractable seizures.

• MeSH
• dítě MeSH
• epilepsie etiologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• mozek růst a vývoj   metabolismus   patologie   MeSH
• nemoci mozku patologie   MeSH
• oocyty MeSH
• receptory GABA-A metabolismus   MeSH
• symportéry metabolismus   MeSH
• tuberózní skleróza genetika   patologie   patofyziologie   MeSH
• Xenopus MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We evaluate the mRNA expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in skeletal muscle (soleus, red and white gastrocnemius), heart and liver tissues in mice submitted to a single bout of swimming exercise at the maximal lactate steady state workload (MLSSw). After 72 h of MLSS test, the animals were submitted to a swimming exercise session for 25 min at individual MLSSw. Tissues and muscle samples were obtained at rest (control, n=5), immediately (n=5), 5 h (n=5) and 10 h (n=5) after exercise for determination of the MCT1 and MCT4 mRNA expression (RT-PCR). The MCT1 mRNA expression in liver increased after 10 h in relation to the control, immediate and 5 h groups, but the MCT4 remained unchanged. The MCT1 mRNA expression in heart increased by 31 % after 10 h when compared to immediate, but no differences were observed in relation to the control group. No significant differences were observed for red gastrocnemius in MCT1 and MCT4 mRNA expression. However, white gastrocnemius increased MCT1 mRNA expression immediately when compared to rest, 5 and 10 h test groups. In soleus muscle, the MCT1 mRNA expression increased immediately, 5 and 10 h after exercise when compared to the control. In relation to MCT4 mRNA expression, the soleus increased immediately and 10 h after acute exercise when compared to the control group. The soleus, liver and heart were the main tissues that showed improved the MCT1 mRNA expression, indicating its important role in controlling MLSS concentration in mice.

• MeSH
• anaerobní práh fyziologie   MeSH
• játra metabolismus   MeSH
• kondiční příprava zvířat metody   MeSH
• kosterní svaly fyziologie   MeSH
• mikro RNA metabolismus   MeSH
• myokard metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• orgánová specificita MeSH
• plavání fyziologie   MeSH
• přenašeče monokarboxylových kyselin genetika   metabolismus   MeSH
• symportéry genetika   metabolismus   MeSH
• tělesná námaha fyziologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The accumulation of glycerol is essential for yeast viability upon hyperosmotic stress. Here we show that the osmotolerant yeast Zygosaccharomyces rouxii has two genes, ZrSTL1 and ZrSTL2, encoding transporters mediating the active uptake of glycerol in symport with protons, contributing to cell osmotolerance and intracellular pH homeostasis. The growth of mutants lacking one or both transporters is affected depending on the growth medium, carbon source, strain auxotrophies, osmotic conditions and the presence of external glycerol. These transporters are localised in the plasma membrane, they transport glycerol with similar kinetic parameters and besides their expected involvement in the cell survival of hyperosmotic stress, they surprisingly both contribute to an efficient survival of hypoosmotic shock and to the maintenance of intracellular pH homeostasis under non-stressed conditions. Unlike STL1 in Sa. cerevisiae, the two Z. rouxii STL genes are not repressed by glucose, but their expression and activity are downregulated by fructose and upregulated by non-fermentable carbon sources, with ZrSTL1 being more influenced than ZrSTL2. In summary, both transporters are highly important, though Z. rouxii CBS 732(T) cells do not use external glycerol as a source of carbon.

• MeSH
• biologický transport MeSH
• delece genu MeSH
• fyziologický stres MeSH
• glycerol metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kultivační média chemie   MeSH
• mikrobiální viabilita MeSH
• organické látky metabolismus   MeSH
• osmoregulace * MeSH
• osmotický tlak MeSH
• regulace genové exprese u hub účinky léků   MeSH
• symportéry genetika   metabolismus   MeSH
• Zygosaccharomyces genetika   růst a vývoj   metabolismus   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recently, we have identified two astrocytic subpopulations in the cortex of GFAP-EGFP mice, in which the astrocytes are visualized by the enhanced green-fluorescent protein (EGFP) under the control of the human glial fibrillary acidic protein (GFAP) promotor. These astrocytic subpopulations, termed high response- (HR-) and low response- (LR-) astrocytes, differed in the extent of their swelling during oxygen-glucose deprivation (OGD). In the present study we focused on identifying the ion channels or transporters that might underlie the different capabilities of these two astrocytic subpopulations to regulate their volume during OGD. Using three-dimensional confocal morphometry, which enables quantification of the total astrocytic volume, the effects of selected inhibitors of K⁺ and Cl⁻ channels/transporters or glutamate transporters on astrocyte volume changes were determined during 20 minute-OGD in situ. The inhibition of volume regulated anion channels (VRACs) and two-pore domain potassium channels (K(2P)) highlighted their distinct contributions to volume regulation in HR-/LR-astrocytes. While the inhibition of VRACs or K(2P) channels revealed their contribution to the swelling of HR-astrocytes, in LR-astrocytes they were both involved in anion/K⁺ effluxes. Additionally, the inhibition of Na⁺-K⁺-Cl⁻ co-transporters in HR-astrocytes led to a reduction of cell swelling, but it had no effect on LR-astrocyte volume. Moreover, employing real-time single-cell quantitative polymerase chain reaction (PCR), we characterized the expression profiles of EGFP-positive astrocytes with a focus on those ion channels and transporters participating in astrocyte swelling and volume regulation. The PCR data revealed the existence of two astrocytic subpopulations markedly differing in their gene expression levels for inwardly rectifying K⁺ channels (Kir4.1), K(2P) channels (TREK-1 and TWIK-1) and Cl⁻ channels (ClC2). Thus, we propose that the diverse volume changes displayed by cortical astrocytes during OGD mainly result from their distinct expression patterns of ClC2 and K(2P) channels.

• MeSH
• astrocyty cytologie   účinky léků   metabolismus   MeSH
• biologické modely MeSH
• chloridové kanály metabolismus   MeSH
• draslíkové kanály metabolismus   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• glukosa nedostatek   MeSH
• kyslík MeSH
• lidé MeSH
• modulátory membránového transportu farmakologie   MeSH
• mozková kůra cytologie   MeSH
• myši transgenní MeSH
• myši MeSH
• pohlavní dimorfismus MeSH
• regulace genové exprese účinky léků   MeSH
• sodík-draslík-chloridové symportéry metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• symportéry metabolismus   MeSH
• velikost buňky účinky léků   MeSH
• vezikulární transportní proteiny pro glutamát metabolismus   MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• techniky in vitro MeSH

• MeSH
• adenom genetika   metabolismus   patologie   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• folikulární adenokarcinom genetika   metabolismus   patologie   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy genetika   metabolismus   patologie   MeSH
• papilární adenokarcinom genetika   metabolismus   patologie   MeSH
• polymerázová řetězová reakce MeSH
• receptory cytoplazmatické a nukleární genetika   metabolismus   MeSH
• receptory thyreotropinu biosyntéza   genetika   MeSH
• regulace genové exprese u nádorů fyziologie   genetika   MeSH
• RNA nádorová genetika   chemie   MeSH
• symportéry genetika   metabolismus   MeSH
• thyreoglobulin metabolismus   MeSH
• trans-aktivátory genetika   metabolismus   MeSH
• transkripční faktory paired box MeSH
• transkripční faktory genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• souhrny MeSH