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91.
Terracciano S Bruno I Bifulco G Avallone E Smith CD Gomez-Paloma L Riccio R 《Bioorganic & medicinal chemistry》2005,13(17):5225-5239
Recently, we described the synthesis and the biological evaluation of three modified analogues of jaspamide (1), a natural cyclodepsipeptide possessing a potent antitumor activity as a consequence of its ability to interfere with actin cytoskeleton. To obtain additional information on the potential pharmacophoric core of the target molecule, which is of fundamental importance to discover new and more effective anticancer products, we decided to explore the biological effects of further structural modifications carried out on the parent molecule. The synthesis and the chemical characterization of six jaspamide analogues (2-7) are reported and their conformational and biological properties are described. 相似文献
92.
93.
González-Iglesias R Elvira G Rodríguez-Navarro JA Vélez M Calero M Pajares MA Gasset M 《FEBS letters》2004,556(1-3):161-166
Cu(2+) binding is so far the best characterized property of the prion protein. This interaction has been mapped to the N-terminal domain of the prion protein where multiple His residues occur largely embedded within the repetitive PHGGGWGQ sequence known as octarepeats. When Cu(2+) interaction is studied using a solution of full-length bovine prion protein containing six octarepeats at protein concentrations above 25 microM, a drastic increase in solution turbidity is observed due to the formation of insoluble cation-protein complexes that appear as bidimensional polymer meshes. These bidimensional meshes consist of a single layer of protein molecules crosslinked by Cu(2+) cations. Polymer formation is a cooperative process that proceeds by nucleation of protein molecules with a Cu(2+) site occupancy of above 2. These results support the hypothesis that the N-terminal domain of prion protein is a ligand binding module that promotes crosslinked assembly, and suggest the existence of inter-repeat Cu(2+) sites. 相似文献
94.
Augmented heme oxygenase-1 induces prostaglandin uptake via the prostaglandin transporter in micro-vascular endothelial cells 总被引:2,自引:0,他引:2
Pucci ML Chakkalakkal B Liclican EL Leedom AJ Schuster VL Abraham NG 《Biochemical and biophysical research communications》2004,323(4):1299-1305
Previous studies show that expression of heme oxygenase-1 (HO-1) in endothelial cells results in decreased cyclooxygenase expression and prostaglandin (PG) levels through limiting heme availability. Regulation of PGs, important inflammatory mediators, may contribute to the anti-inflammatory potential of HO-1. Here we examine the effects of HO-1 expression on PG clearance via the prostaglandin transporter (PGT). Endothelial cells expressing human HO-1 via retroviral transfer exhibit approximately 7-fold higher levels of PGT RNA and equivalently elevated uptake of [(3)H]PGE(2). The pattern and extent of uptake and the substrate inhibitory constants of PGE(2), PGF(2alpha), and thromboxane B(2) are similar to those of cloned PGT. Treatment of cells with stannous chloride, an inducer of HO-1, results in increased expression of PGT while incubation of cells expressing human HO-1 with stannic mesophorphyrin, a substrate inhibitor of HO-1, decreases PG uptake. Therefore, PG clearance via PGT may contribute to the cellular regulation of PG levels by HO-1. 相似文献
95.
Pilar Mateo Esther Berrendero Elvira Perona Virginia Loza Brian A. Whitton 《Hydrobiologia》2010,652(1):255-268
There is increasing evidence that fluvial systems are influenced by anthropogenic factors, and disturbance due to pollution
and other human interference gives rise to specific problems. It is now imperative that we develop and apply novel and effective
ways which allow us to monitor water quality. The present study was planned as part of a programme to develop biological monitoring
methods to assess nutrient characteristics of upland calcareous streams and rivers. Phototrophs respond to environmental changes
over a period of time, so organisms sampled at one time can potentially provide almost as much information about nutrients
in the water as a number of individual chemical measurements. Phosphatase activity is often a good indicator of phosphorus
limitation, and field materials could be used to study changes in nutrients dynamics. The calcareous River Muga, north-east
Spain, at a site 10 km downstream from its source in the Pyrenees, was therefore chosen for the present study of surface phosphatase
activities of the main cyanobacterial communities at different seasons to assess P limitation and establish the suitability
of this method for use in monitoring catchment processes. Here we report seasonal changes of phosphatase activity in field
populations of Schizothrix coriacea, Rivularia biasolettiana, Tolypothrix distorta var. penicillata and Nostoc verrucosum. All four cyanobacteria showed marked surface phosphomonoesterase and phosphodiesterase activity on each sampling period.
Michaelis-Menten kinetic studies showed similar K
m
values for the four species suggesting similar affinity for organic P substrates. Light had no effect on phosphatase activities,
indicating that there is no need to consider this factor in short-term field assays. However, there was an increase in phosphomonoesterase
activity of Rivularia with rise in temperature over the range 10–35°C, which suggests adaptation to the frequent temperature changes in nature.
Phosphorus limitation seems the main chemical factor influencing phototrophs in R. Muga. Combined observations on macroscopically
visible phototrophs with assays of surface phosphatase activity provide a valuable means of assessing long-term changes in
a catchment. 相似文献
96.
97.
Svensjö E Batista PR Brodskyn CI Silva R Lima AP Schmitz V Saraiva E Pesquero JB Mori MA Müller-Esterl W Scharfstein J 《Microbes and infection / Institut Pasteur》2006,8(1):206-220
Kinins, the vasoactive peptides proteolytically liberated from kininogens, were recently recognized as signals alerting the innate immune system. Here we demonstrate that Leishmania donovani and Leishmania chagasi, two etiological agents of visceral leishmaniasis (VL), activate the kinin system. Intravital microscopy in the hamster cheek pouch showed that topically applied promastigotes induced macromolecular leakage (FITC-dextran) through postcapillary venules. Peaking at 15 min, the parasite-induced leakage was drastically enhanced by captopril (Cap), an inhibitor of angiotensin-converting enzyme (ACE), a kinin-degrading metallopeptidase. The enhanced microvascular responses were cancelled by HOE-140, an antagonist of the B2 bradykinin receptor (B2R), or by pre-treatment of promastigotes with the irreversible cysteine proteinase inhibitor N-methylpiperazine-urea-Phe-homoPhe-vinylsulfone-benzene (N-Pip-hF-VSPh). In agreement with the above-mentioned data, the promastigotes vigorously induced edema in the paw of Cap-treated J129 mice, but not Cap-B2R-/- mice. Analysis of parasite-induced breakdown of high molecular weight kininogens (HK), combined with active site-affinity-labeling with biotin-N-Pip-hF-VSPh, identified 35-40 kDa proteins as kinin-releasing cysteine peptidases. We then checked if macrophage infectivity was influenced by interplay between these kinin-releasing parasite proteases, kininogens, and kinin-degrading peptidases (i.e. ACE). Our studies revealed that full-fledged B2R engagement resulted in vigorous increase of L. chagasi uptake by resident macrophages. Evidence that inflammatory macrophages treated with HOE-140 became highly susceptible to amastigote outgrowth, assessed 72 h after initial macrophage interaction, further suggests that the kinin/B2R activation pathway may critically modulate inflammation and innate immunity in visceral leishmaniasis. 相似文献
98.
All identified membrane fusion proteins are transmembrane proteins. In the present study, we explored the post-mitotic reassembly of the NE (nuclear envelope). The proteins that drive membrane rearrangements in NE assembly remain unknown. To determine whether transmembrane proteins are prerequisite components of this fusion machinery, we have focused on nuclear reconstitution in a cell-free system. Mixing of soluble interphase cytosolic extract and MV (membrane vesicles) from amphibian eggs with chromatin results in the formation of functional nuclei. We replaced MV and cytosol with protein-free phosphatidylcholine LS (liposomes) that were pre-incubated with interphase cytosol. While later stages of NE assembly yielding functional nucleus did not proceed without integral proteins of MV, LS-associated cytosolic proteins were sufficient to reconstitute membrane targeting to the chromatin and GTP-dependent lipid mixing. Binding involved LS-associated A-type lamin, and fusion involved Ran GTPase. Thus in contrast with post-fusion stages, fusion initiation in NE assembly, like membrane remodelling in budding and fission, does not require transmembrane proteins. 相似文献
99.
Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome
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Huebner A Mann P Rohde E Kaindl AM Witt M Verkade P Jakubiczka S Menschikowski M Stoltenburg-Didinger G Koehler K 《Molecular and cellular biology》2006,26(5):1879-1887
Triple A syndrome is a human autosomal recessive disorder characterized by adrenal insufficiency, achalasia, alacrima, and neurological abnormalities affecting the central, peripheral, and autonomic nervous systems. In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes. To analyze the function of the gene in the context of the whole organism and in an attempt to obtain an animal model for human triple A syndrome, we generated mice lacking a functional Aaas gene. The Aaas-/- animals were found to be externally indistinguishable from their wild-type littermates, although their body weight was on the average lower than that of wild-type mice. Histological analysis of various tissues failed to reveal any differences between Aaas-/- and wild-type mice. Aaas-/- mice exhibit unexpectedly mild abnormal behavior and only minor neurological deficits. Our data show that the lack of ALADIN in mice does not lead to a triple A syndrome-like disease. Thus, in mice either the function of ALADIN differs from that in humans, its loss can be readily compensated for, or additional factors, such as environmental conditions or genetic modifiers, contribute to the disease. 相似文献
100.
Veshkurova O Golubenko Z Pshenichnov E Arzanova I Uzbekov V Sultanova E Salikhov S Williams HJ Reibenspies JH Puckhaber LS Stipanovic RD 《Phytochemistry》2006,67(21):2376-2379
The isolation and structure of a phytoalexin, malvone A (2-methyl-3-methoxy-5,6-dihydroxy-1,4-naphthoquinone) is reported. Malvone A formation is induced in Malva sylvestris L. by the plant pathogen Verticillium dahliae. In a turbimetric assay for toxicity to V. dahliae, it had an ED50 value of 24 microg/ml. The structure of malvone A was determined by MS and NMR spectroscopy, and by X-ray crystallographic analysis. The X-ray analysis showed water molecules were located in channels that run along the a-axis. 相似文献