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排序方式: 共有368条查询结果,搜索用时 31 毫秒
301.
Ersmark K Nervall M Gutiérrez-de-Terán H Hamelink E Janka LK Clemente JC Dunn BM Gogoll A Samuelsson B Qvist J Hallberg A 《Bioorganic & medicinal chemistry》2006,14(7):2197-2208
The first macrocyclic inhibitor of the Plasmodium falciparum aspartic proteases plasmepsin I, II, and IV with considerable selectivity over the human aspartic protease cathepsin D has been identified. A series of macrocyclic compounds were designed and synthesized. Cyclizations were accomplished using ring-closing metathesis with the second generation Grubbs catalyst. These compounds contain either a 13-membered or a 16-membered macrocycle and incorporate a 1,2-dihydroxyethylene as transition state mimicking unit. The binding mode of this new class of compounds was predicted with automated docking and molecular dynamics simulations, with an estimation of the binding affinities through the linear interaction energy (LIE) method. 相似文献
302.
303.
The expression of neurotrophins and their receptors in the prenatal and adult human testis: evidence for functions in Leydig cells 总被引:2,自引:2,他引:0
Müller D Davidoff MS Bargheer O Paust HJ Pusch W Koeva Y Jezek D Holstein AF Middendorff R 《Histochemistry and cell biology》2006,126(2):199-211
Previous studies have demonstrated local functions for neurotrophins in the developing and mature testis of rodents. To examine whether these signaling molecules are present and also potentially active in the human testis, we characterized immunohistochemically the expression and cellular localization of the known neurotrophins and their receptors during prenatal testicular development as well as in the adult human testis. Results obtained revealed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3 and 4, as well as neurotrophin receptors p75NTR, TrkA, TrkB, and TrkC during testis morphogenesis. These proteins were also detectable in the adult human testis, and their local expression could be confirmed largely by immunoblot and RT-PCR analyses. Remarkably, the Leydig cells were found to represent the predominant neurotrophin/receptor expression sites within both fetal and adult human testes. Functional assays performed with a mouse tumor Leydig cell line revealed that NGF exposure increases cellular steroid production, indicating a role in differentiation processes. These findings support previously-recognized neuronal characteristics of Leydig cells, provide additional evidence for potential roles of neurotrophins during testis morphogenesis and in the mature testis, and demonstrate for the first time a neurotrophin-induced functional activity in Leydig cells. 相似文献
304.
Electron microscopic visualization of fluorescent signals in cellular compartments and organelles by means of DAB-photoconversion 总被引:3,自引:1,他引:2
Meiblitzer-Ruppitsch C Vetterlein M Stangl H Maier S Neumüller J Freissmuth M Pavelka M Ellinger A 《Histochemistry and cell biology》2008,130(2):407-419
In this work, we show the photoconversion of the fluorochromes enhanced green fluorescent protein (EGFP), yellow fluorescent
protein (YFP), and BODIPY into electron dense diaminobenzidine (DAB)-deposits using the examples of five different target
proteins, and the lipid ceramide. High spatial resolution and specificity in the localization of the converted protein-fluorochrome
complexes and the fluorochrome-labelled lipid were achieved by methodical adaptations around the DAB-photooxidation step,
such as fixation, illumination, controlled DAB-precipitation, and osmium postfixation. The DAB-deposits at the plasma membrane
and membranous compartments, such as endoplasmic reticulum and Golgi apparatus in combination with the fine structural preservation
and high membrane contrast enabled differential topographical analyses, and allowed three-dimensional reconstructions of complex
cellular architectures, such as trans-Golgi–ER junctions. On semithin sections the quality, distribution and patterns of the signals were evaluated; defined areas
of interest were used for electron microscopic analyses and correlative microscopy of consecutive ultrathin sections. The
results obtained with the proteins golgin 84 (G-84), protein disulfide isomerase (PDI), scavenger receptor classB type1 (SR-BI),
and γ-aminobutyric acid (GABA) transporter 1 (GAT1), on one hand closely matched with earlier immunocytochemical data and,
on the other hand, led to new information about their subcellular localizations as exemplified by a completely novel sight
on the subcellular distribution and kinetics of the SR-BI, and provided a major base for the forthcoming research. 相似文献
305.
In the biosynthetic-secretory route from the rough endoplasmic reticulum, across the pre-Golgi intermediate compartments,
the Golgi apparatus stacks, trans Golgi network, and post-Golgi organelles, anterograde transport is accompanied and counterbalanced by retrograde traffic
of both membranes and contents. In the physiologic dynamics of cells, retrograde flow is necessary for retrieval of molecules
that escaped from their compartments of function, for keeping the compartments’ balances, and maintenance of the functional
integrities of organelles and compartments along the secretory route, for repeated use of molecules, and molecule repair.
Internalized molecules may be transported in retrograde direction along certain sections of the secretory route, and compartments
and machineries of the secretory pathway may be misused by toxins. An important example is the toxin of Shigella dysenteriae, which has been shown to travel from the cell surface across endosomes, and the Golgi apparatus en route to the endoplasmic
reticulum, and the cytosol, where it exerts its deleterious effects. Most importantly in medical research, knowledge about
the retrograde cellular pathways is increasingly being utilized for the development of strategies for targeted delivery of
drugs to the interior of cells. Multiple details about the molecular transport machineries involved in retrograde traffic
are known; a high number of the molecular constituents have been characterized, and the complicated fine structural architectures
of the compartments involved become more and more visible. However, multiple contradictions exist, and already established
traffic models again are in question by contradictory results obtained with diverse cell systems, and/or different techniques.
Additional problems arise by the fact that the conditions used in the experimental protocols frequently do not reflect the
physiologic situations of the cells. Regular and pathologic situations often are intermingled, and experimental treatments
by themselves change cell organizations. This review addresses physiologic and pathologic situations, tries to correlate results
obtained by different cell biologic techniques, and asks questions, which may be the basis and starting point for further
investigations. 相似文献
306.
307.
Leitner K Ellinger A Zimmer KP Ellinger I Fuchs R 《Histochemistry and cell biology》2002,117(2):187-193
The non-covalent association of beta 2-microglobulin with MHC class I molecules and MHC class I-type molecules such as FcRn or the hemochromatosis protein (HFE) is of major importance for their function, i.e., antigen presentation, IgG transport, and regulation of iron uptake, respectively. In the human hemochorial placenta, the syncytiotrophoblast forms a continuous epithelial layer covering the villous trees, where it directly contacts maternal blood and, among many other functions, mediates uptake of maternal IgG and iron. The villous syncytiotrophoblast lacks MHC class I molecules but expresses FcRn and HFE. Since data on beta 2-microglobulin synthesis and localization in the term villous syncytiotrophoblast were contradictory, we investigated the subcellular localization of beta 2-microglobulin by immunoelectron microscopy. Synthesis in the trophoblast is demonstrated by colocalization of beta 2-microglobulin with protein disulfide isomerase, a marker protein of the endoplasmic reticulum. The presence of beta 2-microglobulin at the apical plasma membrane corresponds to the recently observed association of beta 2-microglobulin with HFE and FcRn. Localization of beta 2-microglobulin in late endosomes/lysosomes, labeled with antibodies to lysosome membrane antigen LAMP 2, suggests also a degradative route of beta 2-microglobulin internalized by fluid-phase from the maternal blood. 相似文献
308.
Is 1-hydroxypyrene a reliable bioindicator of measured dietary polycyclic aromatic hydrocarbon under normal conditions? 总被引:3,自引:0,他引:3
Viau C Diakité A Ruzgyté A Tuchweber B Blais C Bouchard M Vyskocil A 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,778(1-2):165-177
Five healthy volunteers consumed similar amounts of identical foods for 5 consecutive days. The concentration of pyrene and of benzo(a)pyrene was determined in each of the 15 meals by a short analytical method that included sample saponification, solvent extraction, and HPLC analysis. The volunteers also provided three daily total volume 8-h urine samples for the duration of the study for the assessment of 1-hydroxypyrene, a biomarker of pyrene and polycyclic aromatic hydrocarbon (PAH) exposure. Mean recoveries were 83 and 75%, respectively, for pyrene and benzo(a)pyrene in food. Daily dietary pyrene doses varied from 0.7 to 3 microg. Excluding two outliers consisting of meals containing charbroiled pork and beef, pyrene content in the meals estimated from the published literature data was correlated to the measured pyrene, but overestimated the actual concentration by ca. 70%. Despite the identical ingested doses of pyrene, there was a 50-76% (coefficient of variation) interindividual variability in the daily-excreted amount of 1-hydroxypyrene. Urinary excretion of this metabolite was not correlated with ingested dose of pyrene under the normal feeding conditions used in this study. Bioavailability, enzymatic polymorphism, and differences in enterohepatic cycling of the metabolite may contribute to the observed variability. It was calculated that dietary pyrene intake accounts for between 87.5 and 99.8% of the sum of dietary and inhalation intake. From the presented data, unless the above-mentioned factors are taken into account, 1-hydroxypyrene might not be a reliable bioindicator of ingested pyrene (PAHs) under normal feeding conditions. 相似文献
309.
Brefeldin A-regulated retrograde transport into the endoplasmic reticulum of internalised wheat germ agglutinin 总被引:5,自引:5,他引:0
Vetterlein M Niapir M Ellinger A Neumüller J Pavelka M 《Histochemistry and cell biology》2003,120(2):121-128
The effects of the fungal metabolite brefeldin A (BFA) on the endocytic routes of internalised wheat germ agglutinin (WGA) were studied in human HepG2 hepatoma cells, drawing particular attention to the application times in relation to the membrane dynamics occurring at the trans Golgi face during endocytosis. As shown in previous studies, transport of internalised WGA into the Golgi apparatus can be classified in three stages being characterised by predominance of vesicular endosomes (stage I), formation of an extended endocytic trans Golgi network (stage II) and uptake of WGA into the stacked Golgi cisternae (stage III). BFA treatment of the cells led to rapid tubular-reticular transformations of the Golgi stacks. Retrograde transport and further destinations of internalised WGA depended on the time of BFA application. When BFA was administered during stages I or II, WGA was localised within the BFA-induced tubules and networks, but never was found within the endoplasmic reticulum. By contrast, BFA treatment during stage III led to a redistribution of internalised WGA into cisternae of the endoplasmic reticulum. These results show that BFA administered according to a precise time schedule can be used as a regulatory agent that allows to control retrograde traffic of internalised molecules into the endoplasmic reticulum. 相似文献
310.
Fratzl-Zelman N Glantschnig H Rumpler M Nader A Ellinger A Varga F 《Cell biology international》2003,27(6):459-468
Matrix metalloproteinase-13 (MMP-13), is a key protein of bone matrix degradation, and is highly expressed by osteoblasts. We used the osteoblast-like MC3T3-E1 cell line and compared the stimulatory effects of the bone resorptive agents 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) 3,3',5-triido-L-thyronine (T3) on the expression of MMP-13 mRNA. We showed that the stimulatory effects were time and dose dependent, and were also transduced to the protein level, with 1,25-(OH)(2)D(3)being more potent.MMP-13 expression in different mouse cells and its localization within developing bone from the onset of osteogenesis were also investigated. 1,25-(OH)(2)D(3)- and T3-regulated osteocalcin (Osc) expression in mouse osteoblasts was compared to hormonal effects on MMP-13 expression and activity. Here we show divergent and common roles of 1,25-(OH)(2)D(3)and T3 action on the expression of these marker proteins, depending on the stage of cell differentiation. In addition, we propose a role for MMP-13 in the bone collar of developing long bones. The results could help to more precisely characterize hormonal regulation in the developmental sequence of osteoblasts. 相似文献