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141.
Benet M Dulman RY Suzme R de Miera EV Vega ME Nguyen T Zavadil J Pellicer A 《Journal of cellular physiology》2012,227(6):2341-2351
Previously, we have shown that wild type N-ras (wt N-ras) harbors an anti-malignant effect against mutated Ras and in tumors without Ras mutations. To investigate the molecular bases of this anti-malignant activity, we have studied the potency of this anti-malignant effect in a model system against SV40 large T antigen (SV40T). We show that wild-type N-ras (wt N-ras) counteracts the effects of SV40T in NIH3T3 cells as seen by a decrease in proliferation, anchorage independence and changes in migration. We also show that wt N-ras elicits the same anti-malignant effects in some human tumor cell lines (HT1080 and MDA-MB-231). Through mRNA and microRNA (miRNAs) expression profiling we have identified genes (decorin) and miRNAs (mir-29A, let-7b) modulated by wt N-ras potentially responsible for the anti-malignant effect. Wt N-ras appears to mediate its anti-malignant effect by downregulating some of the targets of the TGFβ pathway and decorin, which are able to reverse the inhibition of migration induced by wt N-ras. Our experiments show that the molecules that mediate the anti-malignant effect by wt N-ras appear to be different from those modulated by transforming N-ras. The components of the pathways modulated by wt N-ras mediating its anti-malignant effects are potential targets for therapeutic intervention in cancer. 相似文献
142.
An enzymatic reactor with lipase immobilized on a monolithic polymer support has been prepared and used to catalyze the transesterification of triacylglycerides into the fatty acid methyl esters commonly used for biodiesel. A design of experiments procedure was used to optimize the monolithic reactor with variables including control of the surface polarity of the monolith via variations in the length of the hydrocarbon chain in alkyl methacrylate monomer, time of grafting of 1-vinyl-4,4-dimethylazlactone used to activate the monolith, and time used for the immobilization of porcine lipase. Optimal conditions involved the use of a poly(stearyl methacrylate-co-ethylene dimethacrylate) monolith, grafted first with vinylazlactone, then treated with lipase for 2 h to carry out the immobilization of the enzyme. Best conditions for the transesterification of glyceryl tributyrate included a temperature of 37°C and a 10 min residence time of the substrate in the bioreactor. The reactor did not lose its activity even after pumping through it a solution of substrate equaling 1,000 reactor volumes. This enzymatic reactor was also used for the transesterification of triacylglycerides from soybean oil to fatty acid methyl esters thus demonstrating the ability of the reactor to produce biodiesel. 相似文献
143.
Insulin and insulin-like growth factor II differentially regulate endocytic sorting and stability of insulin receptor isoform A 总被引:1,自引:0,他引:1
Morcavallo A Genua M Palummo A Kletvikova E Jiracek J Brzozowski AM Iozzo RV Belfiore A Morrione A 《The Journal of biological chemistry》2012,287(14):11422-11436
The insulin receptor isoform A (IR-A) binds both insulin and insulin-like growth factor (IGF)-II, although the affinity for IGF-II is 3-10-fold lower than insulin depending on a cell and tissue context. Notably, in mouse embryonic fibroblasts lacking the IGF-IR and expressing solely the IR-A (R-/IR-A), IGF-II is a more potent mitogen than insulin. As receptor endocytosis and degradation provide spatial and temporal regulation of signaling events, we hypothesized that insulin and IGF-II could affect IR-A biological responses by differentially regulating IR-A trafficking. Using R-/IR-A cells, we discovered that insulin evoked significant IR-A internalization, a process modestly affected by IGF-II. However, the differential internalization was not due to IR-A ubiquitination. Notably, prolonged stimulation of R-/IR-A cells with insulin, but not with IGF-II, targeted the receptor to a degradative pathway. Similarly, the docking protein insulin receptor substrate 1 (IRS-1) was down-regulated after prolonged insulin but not IGF-II exposure. Similar results were also obtained in experiments using [NMeTyr(B26)]-insulin, an insulin analog with IR-A binding affinity similar to IGF-II. Finally, we discovered that IR-A was internalized through clathrin-dependent and -independent pathways, which differentially regulated the activation of downstream effectors. Collectively, our results suggest that a lower affinity of IGF-II for the IR-A promotes lower IR-A phosphorylation and activation of early downstream effectors vis à vis insulin but may protect IR-A and IRS-1 from down-regulation thereby evoking sustained and robust mitogenic stimuli. 相似文献
144.
Poreba M Gajda A Picha J Jiracek J Marschner A Klein CD Salvesen GS Drag M 《Biochimie》2012,94(3):704-710
Methionyl aminopeptidases (MetAPs) are metallo-dependent proteases responsible for removing of N-terminal methionine residue of peptides and proteins during protein maturation and activation. In this report we use a comprehensive strategy to screen the substrate specificity of three methionyl aminopeptidases: Homo sapiens MetAP-1, Homo sapiens MetAP-2 and Escherichia coli MetAP-1. By utilizing a 65-membered fluorogenic substrate library consisting of natural and unnatural amino acids we established detailed substrate preferences of each enzyme in the S1 pocket. Our results show that this pocket is highly conserved for all investigated MetAPs, very stringent for methionine, and that several unnatural amino acids with methionine-like characteristics were also well hydrolyzed by MetAPs. The substrate-derived results were verified using several phosphonate and phosphinate-based inhibitors. 相似文献
145.
146.
Pikula J Bandouchova H Novotny L Meteyer CU Zukal J Irwin NR Zima J Martínková N 《Journal of wildlife diseases》2012,48(1):207-211
White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans. 相似文献
147.
The conventional stoichiometry of the oxidation of elemental sulfur by ferric iron in Acidithiobacillus ferrooxidans was not in agreement with our experimental data in terms of ferrous iron and proton formation. Reaction modelling under the
actual conditions of bacterial activity resulted in a different stoichiometry, where additional iron species participate in
the process to affect the number of released protons. The suggested reaction equation may more accurately predict the intensity
of environmental acidification during the anaerobic bioprocess. 相似文献
148.
149.
Long TE Lu X Galizzi M Docampo R Gut J Rosenthal PJ 《Bioorganic & medicinal chemistry letters》2012,22(8):2976-2979
Phosphonium lipocations were synthesized and evaluated for inhibition of the development of Plasmodium falciparum and Trypanosoma cruzi, etiological agents of malaria and Chagas disease, respectively. Optimal phthalimides and 1,4-naphthoquinone-based lipocations were active in vitro at mid-high nM concentrations against P. falciparum and low μM concentrations against T. cruzi. 相似文献
150.
Otakar Rop Jiri Mlcek Tunde Jurikova Magdalena Valsikova 《Central European Journal of Biology》2012,7(4):672-679
At present, Cape gooseberry (Physalis peruviana) fruit is one of the less used raw materials of plant origin, which can be used for human nutrition. This fruit, as well
as alimentary products made of it, were used by healers in folk medicine in the distant past. The aim of this study was to
monitor and evaluate the antioxidant capacity of fresh fruit of three Cape gooseberry cultivars ‘Giant’, ‘Golden berry’ and
‘Inka’. Antioxidant capacity was also tested, on the basis of the scavenging effect of reactive oxygen species (ROS) and lipid
peroxidation of methanolic extracts made of fresh fruit. These results were further extended and supplemented with determinates
of the vitamin C and total phenolic contents. These analyses were made for three consecutive years. The highest values of
antioxidant capacity were observed in the ‘Inka’ cultivar (9.31 grams of ascorbic acid equivalents kg−1 of fresh mass). In this cultivar, the obtained results were corroborated also in ROS and the contents of vitamin C and total
phenolics. Due to a high antioxidant capacity of this fruit species, the results presented should increase its popularity
above all as a promising raw material, which can be used for human nutrition. 相似文献