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31.
Neckár J Marková I Novák F Nováková O Szárszoi O Ost'ádal B Kolár F 《American journal of physiology. Heart and circulatory physiology》2005,288(4):H1566-H1572
We examined the role of protein kinase C (PKC) in the cardioprotective mechanism induced by long-term adaptation to chronic intermittent hypoxia. Adult male Wistar rats were exposed to hypobaric hypoxia of 7,000 m for 8 h/day, 5 days/wk; the total number of exposures was 24-32. A control group was kept under normoxic conditions. Western blot analysis of PKC isoforms-delta and -epsilon was performed in the cytosol and three particulate fractions of left ventricular myocardium. Infarct size was determined in open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion. The PKC inhibitors chelerythrine (1 or 5 mg/kg) or rottlerin (selective for PKC-delta isoform; 0.3 mg/kg) were administered intravenously as a single bolus 15 min before ischemia. Chronic hypoxia had no effect on the expression and distribution of PKC-epsilon. The relative amount of PKC-delta increased in the cytosol and nuclear-cytoskeletal, mitochondrial, and microsomal fractions of chronically hypoxic myocardium by 100%, 212%, 237%, and 146%, respectively, compared with corresponding normoxic values. Chronic hypoxia decreased the size of myocardial infarction (normalized to the area at risk) by about one-third on the average (P < 0.05). Both doses of chelerythrine tended to reduce infarction in controls, and only the high dose completely abolished the improvement of ischemic tolerance in hypoxic hearts (P < 0.05). Rottlerin attenuated the infarct size-limiting effect of chronic hypoxia (P < 0.05), and it had no effect in controls. These results suggest that chronic intermittent hypoxia-induced cardioprotection in rats is partially mediated by PKC-delta; the contribution of other isoforms remains to be determined. 相似文献
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Petrlová J Blastík O Průsa R Kukacka J Potĕsil D Mikelová R Adam V Zehnálek J Kizek R 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2005,149(2):485-488
Metallothioneins belong to the group of intracellular, high molecular and cysteine-rich proteins whose content increase with increasing concentration of a heavy metal. Here we applied the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothionein in human blood serum of patient poisoned by lead and/or treated by platinum. The increased metallothionein concentrations in both cases were observed. 相似文献
33.
The bkdR gene of Streptomyces coelicolor is required for morphogenesis and antibiotic production and encodes a transcriptional regulator of a branched-chain amino acid dehydrogenase complex 下载免费PDF全文
Sprusansky O Stirrett K Skinner D Denoya C Westpheling J 《Journal of bacteriology》2005,187(2):664-671
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Zvarec O Polyak SW Tieu W Kuan K Dai H Pedersen DS Morona R Zhang L Booker GW Abell AD 《Bioorganic & medicinal chemistry letters》2012,22(8):2720-2722
Herein we outline the antibacterial activity of amino acid containing thiazolidinediones and rhodanines against Gram-positive bacteria Staphylococcus aureus ATCC 31890, Staphylococcus epidermidis and Bacillus subtilis ATCC 6633. The rhodanine derivatives were generally more active than the analogous thiazolidinediones. Compounds of series 5 showed some selectivity for Bacillus subtilis ATCC 6633, the extent of which is enhanced by the inclusion of a non-polar amino acid at the 5-position of the core thiazolidinediones and rhodanines scaffolds. SAR data of series 8 demonstrated improved activity against the clinically more significant Staphylococci with selectivity over Bacillus subtilis ATCC 6633 induced by introduction of a bulky aryl substituent at the 5-position of the core scaffolds. 相似文献
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Est1 and Ebs1 in Saccharomyces cerevisiae are paralogous proteins that arose through whole-genome duplication and that serve distinct functions in telomere maintenance and translational regulation. Here we present our functional analysis of the sole Est1/Ebs1 homologue in the related budding yeast Kluyveromyces lactis (named KlEst1). We show that similar to other Est1s, KlEst1 is required for normal telomere maintenance in vivo and full telomerase primer extension activity in vitro. KlEst1 also associates with telomerase RNA (Ter1) and an active telomerase complex in cell extracts. Both the telomere maintenance and the Ter1 association functions of KlEst1 require its N-terminal domain but not its C terminus. Analysis of clusters of point mutations revealed residues in both the N-terminal TPR subdomain and the downstream helical subdomain (DSH) that are important for telomere maintenance and Ter1 association. A UV cross-linking assay was used to establish a direct physical interaction between KlEst1 and a putative stem-loop in Ter1, which also requires both the TPR and DSH subdomains. Moreover, similar to S. cerevisiae Ebs1 (ScEbs1) (but not ScEst1), KlEst1 confers rapamycin sensitivity and may be involved in nonsense-mediated decay. Interestingly, unlike telomere regulation, this apparently separate function of KlEst1 requires its C-terminal domain. Our findings provide insights on the mechanisms and evolution of Est1/Ebs1 homologues in budding yeast and present an attractive model system for analyzing members of this multifunctional protein family. 相似文献
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The choice of tools that enable efficient targeting of exogenous antigens (Ag) for processing and presentation by professional Ag-presenting cells (APC) remains limited. This represents, indeed, a bottleneck in development of vaccines inducing specific T-cell responses. Here, we describe a novel strategy of Ag delivery into APCs. The Ag of choice is fused to the N- or C-terminus of streptavidin (SA) and tetrameric Ag-SA or SA-Ag fusion proteins are produced in E. coli and purified by 2-Iminobiotin-Agarose affinity chromatography. Alternatively, Ag-SA proteins are purified from urea extracts of E. coli inclusion bodies and refolded in vitro into functional tetramers. Complexes with biotinylated antibodies targeting cell surface receptors are formed and used to deliver the Ags of choice for processing and presentation by APCs and induction of Ag-specific CD4+ and CD8+ T-cell responses in vitro and in vivo. 相似文献
40.
Lameignere E Malinovská L Sláviková M Duchaud E Mitchell EP Varrot A Sedo O Imberty A Wimmerová M 《The Biochemical journal》2008,411(2):307-318
Chronic colonization of the lungs by opportunist bacteria such as Pseudomonas aeruginosa and members of the Bcc (Burkholderia cepacia complex) is the major cause of morbidity and mortality among CF (cystic fibrosis) patients. PA-IIL (lecB gene), a soluble lectin from Ps. aeruginosa, has been the subject of much interest because of its very strong affinity for fucose. Orthologues have been identified in the opportunist bacteria Ralstonia solanacearum, Chromobacterium violaceum and Burkholderia of Bcc. The genome of the J2315 strain of B. cenocepacia, responsible for epidemia in CF centres, contains three genes that code for proteins with PA-IIL domains. The shortest gene was cloned in Escherichia coli and pure recombinant protein, BclA (B. cenocepacia lectin A), was obtained. The presence of native BclA in B. cenocepacia extracts was checked using a proteomic approach. The specificity of recombinant BclA was characterized using surface plasmon resonance showing a preference for mannosides and supported with glycan array experiments demonstrating a strict specificity for oligomannose-type N-glycan structures. The interaction thermodynamics of BclA with methyl alpha-D-mannoside demonstrates a dissociation constant (K(d)) of 2.75 x 10(-6) M. The X-ray crystal structure of the complex with methyl alpha-D-mannoside was determined at 1.7 A (1 A=0.1 nm) resolution. The lectin forms homodimers with one binding site per monomer, acting co-operatively with the second dimer site. Each monomer contains two Ca2+ ions and one sugar ligand. Despite strong sequence similarity, the differences between BclA and PA-IIL in their specificity, binding site and oligomerization mode indicate that the proteins should have different roles in the bacteria. 相似文献