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151.
Hallmann A Klimek J Masaoka M Kamiński M Kedzior J Majczak A Niemczyk E Woźniak M Trzonkowski P Wakabayashi T 《Acta biochimica Polonica》2004,51(4):1023-1038
Characterization of free radical-induced cell injury processes of placenta cells is of vital importance for clinical medicine for the maintenance of intrauterine fetal life. The present study has analyzed cell injury processes in cells of the choriocarcinoma cell line JAR treated with menadione, an anticancer drug, and H(2)O(2) in comparison to osteosarcoma 143B cells using electron microscopic and flow cytometric techniques. Flow cytometry on JAR cells exposed to 100 muM menadione and double-stained with Annexin V and propidium iodide (PI) detected apoptotic cells reaching the maximum after 4 h of incubation with a rapid decrease thereafter. Viable cells became decreased to 46% of the control after 2 h of incubation, reaching 5% after 4 h. Cells stainable with both Annexin V and PI began to increase distinctly after 2 h of incubation, reaching 55% after 4 h. Electron microscopy showed that cells stainable with both dyes specified above had condensed nuclei and swollen cytoplasm, suggesting that they were undergoing a switch of the cell death mode from apoptosis to necrosis. On the other hand, 90% of 143B cells remained intact after 4 h of menadione treatment although the intracellular levels of superoxide were always higher than those of JAR cells treated with the drug. In contrast, JAR cells were more resistant than 143B cells to H(2)O(2)-induced cytotoxicity. These results may suggest that cytotoxicity of menadione cannot be explained simply by oxygen free radicals generated from the drug. The resistance of JAR cells to oxygen free radical-induced cytotoxicity may be advantageous for intrauterine fetal life. 相似文献
152.
Sobota A Strzelecka-Kiliszek A Gładkowska E Yoshida K Mrozińska K Kwiatkowska K 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(7):4450-4457
Fc gammaR mediate the phagocytosis of IgG-coated particles and the clearance of IgG immune complexes. By dissecting binding from internalization of the particles, we found that the binding stage, rather than particle internalization, triggered tyrosine phosphorylation of Fc gammaR and accompanying proteins. High amounts of Lyn kinase were found to associate with particles isolated at the binding stage from J774 cells. PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), an Src kinase inhibitor, but not piceatannol, an inhibitor of Syk kinase, reduced the amount of Lyn associated with the bound particles and simultaneously diminished the binding of IgG-coated particles. Studies of baby hamster kidney cells transfected with wild-type and mutant Fc gammaRIIA revealed that the ability of the receptor to bind particles was significantly reduced when phosphorylation of the receptor was abrogated by Y298F substitution in the receptor signaling motif. Under these conditions, binding of immune complexes of aggregated IgG was depressed to a lesser extent. A similar effect was exerted on the binding ability of wild-type Fc gammaRIIA by PP2. Moreover, expression of mutant kinase-inactive Lyn K275R inhibited both Fc gammaRIIA phosphorylation and IgG-opsonized particle binding. To gain insight into the mechanism by which protein tyrosine phosphorylation can control Fc gammaR-mediated binding, we investigated the efficiency of clustering of wild-type and Y298F-substituted Fc gammaRIIA upon binding of immune complexes. We found that a lack of Fc gammaRIIA phosphorylation led to an impairment of receptor clustering. The results indicate that phosphorylation of Fc gammaR and accompanying proteins, dependent on Src kinase activity, facilitates the clustering of activated receptors that is required for efficient particle binding. 相似文献
153.
Karolina Kaźmińska Ewelina Hallmann Anna Rusaczonek Aleksandra Korzeniewska Mirosław Sobczak Joanna Filipczak Karol Seweryn Kuczerski Jarosław Steciuk Monika Sitarek-Andrzejczyk Marek Gajewski Katarzyna Niemirowicz-Szczytt Grzegorz Bartoszewski 《Molecular breeding : new strategies in plant improvement》2018,38(9):114
The high content of carotenoids, sugars, dry matter, vitamins and minerals makes the fruit of winter squash (Cucurbita maxima Duchesne) a valuable fresh-market vegetable and an interesting material for the food industry. Due to their nutritional value, long shelf-life and health protective properties, winter squash fruits have gained increased interest from researchers in recent years. Despite these advantages, the genetic and genomic resources available for C. maxima are still limited. The aim of this study was to use the genetic mapping approach to map the ovary colour locus and to identify the quantitative trait loci (QTLs) for high carotenoid content and flesh colour. An F6 recombinant inbred line (RIL) mapping population was developed and used for evaluations of ovary colour, carotenoid content and fruit flesh colour. SSR markers and DArTseq genotyping-by-sequencing were used to construct an advanced genetic map that consisted of 1824 molecular markers distributed across linkage groups corresponding to 20 chromosomes of C. maxima. Total map length was 2208 cM and the average distance between markers was 1.21 cM. The locus affecting ovary colour was mapped at the end of chromosome 14. The identified QTLs for carotenoid content in the fruit and fruit flesh colour shared locations on chromosomes 2, 4 and 14. QTLs on chromosomes 2 and 4 were the most meaningful. A correlation was clearly confirmed between fruit flesh colour as described by the chroma value and carotenoid content in the fruit. A high-density genetic map of C. maxima with mapped loci for important fruit quality traits is a valuable resource for winter squash improvement programmes. 相似文献
154.
Association between single nucleotide polymorphisms of TPH1 and TPH2 genes,and depressive disorders 下载免费PDF全文
Paulina Wigner Piotr Czarny Ewelina Synowiec Michał Bijak Katarzyna Białek Monika Talarowska Piotr Galecki Janusz Szemraj Tomasz Sliwinski 《Journal of cellular and molecular medicine》2018,22(3):1778-1791
Tryptophan catabolites pathway disorders are observed in patients with depression. Moreover, single nucleotide polymorphisms of tryptophan hydroxylase genes may modulate the risk of depression occurrence. The objective of our study was to confirm the association between the presence of polymorphic variants of TPH1 and TPH2 genes, and the development of depressive disorders. Six polymorphisms were selected: c.804‐7C>A (rs10488682), c.‐1668T>A (rs623580), c.803+221C>A (rs1800532), c.‐173A>T (rs1799913)—TPH1, c.‐1449C>A (rs7963803), and c.‐844G>T (rs4570625)—TPH2. A total of 510 DNA samples (230 controls and 280 patients) were genotyped using TaqMan probes. Among the studied polymoorphisms, the G/G genotype and G allele of c.804‐7C>A—TPH1, the T/T homozygote of c.803+221C>A—TPH1, the A/A genotype and A allele of c.1668T>A—TPH1, the G/G homozygote and G allele of c.‐844G>T—TPH2, and the C/A heterozygote and A allele of c.‐1449C>A—TPH2 were associated with the occurrence of depression. However, the T/T homozygote of c.‐1668T>A—TPH1, the G/T heterozygote and T allele of c.‐844G>T—TPH2, and the C/C homozygote and C allele of c.‐1449C>A—TPH2 decreased the risk of development of depressive disorders . Each of the studied polymorphisms modulated the risk of depression for selected genotypes and alleles. These results support the hypothesis regarding the involvement of the pathway in the pathogenesis of depression. 相似文献
155.
Sebastian Pintscher Patryk Kuleta Ewelina Cieluch Arkadiusz Borek Marcin Sarewicz Artur Osyczka 《The Journal of biological chemistry》2016,291(13):6872-6881
In biological energy conversion, cross-membrane electron transfer often involves an assembly of two hemes b. The hemes display a large difference in redox midpoint potentials (ΔEm_b), which in several proteins is assumed to facilitate cross-membrane electron transfer and overcome a barrier of membrane potential. Here we challenge this assumption reporting on heme b ligand mutants of cytochrome bc1 in which, for the first time in transmembrane cytochrome, one natural histidine has been replaced by lysine without loss of the native low spin type of heme iron. With these mutants we show that ΔEm_b can be markedly increased, and the redox potential of one of the hemes can stay above the level of quinone pool, or ΔEm_b can be markedly decreased to the point that two hemes are almost isopotential, yet the enzyme retains catalytically competent electron transfer between quinone binding sites and remains functional in vivo. This reveals that cytochrome bc1 can accommodate large changes in ΔEm_b without hampering catalysis, as long as these changes do not impose overly endergonic steps on downhill electron transfer from substrate to product. We propose that hemes b in this cytochrome and in other membranous cytochromes b act as electronic connectors for the catalytic sites with no fine tuning in ΔEm_b required for efficient cross-membrane electron transfer. We link this concept with a natural flexibility in occurrence of several thermodynamic configurations of the direction of electron flow and the direction of the gradient of potential in relation to the vector of the electric membrane potential. 相似文献
156.
157.
158.
Dorota Łażewska Maria Kaleta Stefanie Hagenow Szczepan Mogilski Gniewomir Latacz Tadeusz Karcz Annamaria Lubelska Ewelina Honkisz Jadwiga Handzlik David Reiner Grzegorz Satała Barbara Filipek Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2018,26(9):2573-2585
A series of 1- and 2-naphthyloxy derivatives were synthesized and evaluated for histamine H3 receptor affinity. Most compounds showed high affinities with Ki values below 100?nM. The most potent ligand, 1-(5-(naphthalen-1-yloxy)pentyl)azepane (11) displayed high affinity for the histamine H3 receptor with a Ki value of 21.9?nM. The antagonist behaviour of 11 was confirmed both in vitro in the cAMP assay (IC50?=?312?nM) and in vivo in the rat dipsogenia model (ED50?=?3.68?nM). Moreover, compound 11 showed positive effects on scopolamine induced-memory deficits in mice (at doses of 10 and 15?mg/kg) and an analgesic effect in the formalin test in mice with ED50?=?30.6?mg/kg (early phase) and ED50?=?20.8?mg/kg (late phase). Another interesting compound, 1-(5-(Naphthalen-1-yloxy)pentyl)piperidine (13; H3R Ki?=?53.9?nM), was accepted for Anticonvulsant Screening Program at the National Institute of Neurological Disorders and Stroke/National Institute of Health (Rockville, USA). The screening was performed in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole (scPTZ) and the 6-Hz psychomotor animal models of epilepsy. Neurologic deficit was evaluated by the rotarod test. Compound 13 inhibited convulsions induced by the MES with ED50 of 19.2?mg/kg (mice, i.p.), 17.8 (rats, i.p.), and 78.1 (rats, p.o.). Moreover, 13 displayed protection against the 6-Hz psychomotor seizures (32?mA) in mice (i.p.) with ED50 of 33.1?mg/kg and (44?mA) ED50 of 57.2?mg/kg.Furthermore, compounds 11 and 13 showed in vitro weak influence on viability of tested cell lines (normal HEK293, neuroblastoma IMR-32, hepatoma HEPG2), weak inhibition of CYP3A4 activity, and no mutagenicity. Thus, these compounds may be used as leads in a further search for histamine H3 receptor ligands with promising in vitro and in vivo activity. 相似文献
159.
Brain induces the expression of an early cell surface marker for blood-brain barrier-specific endothelium. 总被引:10,自引:1,他引:9 下载免费PDF全文
Capillaries derived from the perineural vascular plexus invade brain tissue early in embryonic development. Considerably later they differentiate into blood-brain barrier (BBB)-forming blood vessels. In the chick, the BBB as defined by impermeability for the protein horseradish peroxidase develops around embryonic day 13. We have previously found that brain endothelial cells start to express a number of proteins at around the same time, suggesting that these proteins play a role in BBB function. Here we describe a 74 kd protein defined by the monoclonal antibody HT7 that is expressed on the surface of chick embryonic blood cells and brain endothelial but on no other endothelial cells. This protein is not detectable on early embryonic brain endothelium, but is expressed by these cells on embryonic day 10. It is absent in choroid plexus endothelial cells which represent permeable fenestrated endothelial cells. The antigen is expressed on choroid plexus epithelium which is the site of the blood-cerebrospinal fluid barrier. Since it is also found in basolateral membranes of kidney tubules, it may be involved in specific carrier mechanisms. Embryonic mouse brain tissue transplanted on the chick chorio-allantoic membrane induces the expression of this antigen on endothelial cells derived from the chorio-allantois. Brain tissue can therefore induce in endothelial cells in vivo the expression of a molecule characteristic of brain endothelium. 相似文献
160.
Carbon and sulfur isotopic signatures of ancient life and environment at the microbial scale: Neoarchean shales and carbonates 下载免费PDF全文
K. H. Williford T. Ushikubo K. Lepot K. Kitajima C. Hallmann M. J. Spicuzza R. Kozdon J. L. Eigenbrode R. E. Summons J. W. Valley 《Geobiology》2016,14(2):105-128
An approach to coordinated, spatially resolved, in situ carbon isotope analysis of organic matter and carbonate minerals, and sulfur three‐ and four‐isotope analysis of pyrite with an unprecedented combination of spatial resolution, precision, and accuracy is described. Organic matter and pyrite from eleven rock samples of Neoarchean drill core express nearly the entire range of δ13C, δ34S, Δ33S, and Δ36S known from the geologic record, commonly in correlation with morphology, mineralogy, and elemental composition. A new analytical approach (including a set of organic calibration standards) to account for a strong correlation between H/C and instrumental bias in SIMS δ13C measurement of organic matter is identified. Small (2–3 μm) organic domains in carbonate matrices are analyzed with sub‐permil accuracy and precision. Separate 20‐ to 50‐μm domains of kerogen in a single ~0.5 cm3 sample of the ~2.7 Ga Tumbiana Formation have δ13C = ?52.3 ± 0.1‰ and ?34.4 ± 0.1‰, likely preserving distinct signatures of methanotrophy and photoautotrophy. Pyrobitumen in the ~2.6 Ga Jeerinah Formation and the ~2.5 Ga Mount McRae Shale is systematically 13C‐enriched relative to co‐occurring kerogen, and associations with uraniferous mineral grains suggest radiolytic alteration. A large range in sulfur isotopic compositions (including higher Δ33S and more extreme spatial gradients in Δ33S and Δ36S than any previously reported) are observed in correlation with morphology and associated mineralogy. Changing systematics of δ34S, Δ33S, and Δ36S, previously investigated at the millimeter to centimeter scale using bulk analysis, are shown to occur at the micrometer scale of individual pyrite grains. These results support the emerging view that the dampened signature of mass‐independent sulfur isotope fractionation (S‐MIF) associated with the Mesoarchean continued into the early Neoarchean, and that the connections between methane and sulfur metabolism affected the production and preservation of S‐MIF during the first half of the planet's history. 相似文献