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991.
The possible hydrolysis of substance P (Arg–Pro–Lys–Pro–Gln–Gln–Phe–Phe–Gly–Leu–Met) in presence of the osteoblastic cell
line SaOS-2 was measured by capillary electrophoresis coupled to mass detection. The results obtained indicate that a very
rapid disappearance of the intact undecapeptide was associated to a slower appearance of seven of its eight component amino
acids. These results can be interpreted as indicating that an extremely fast hydrolysis of substance P by endopeptidases,
which released peptidic by-products, was followed by a noticeably slower secondary degradation which released free amino acids.
In decreasing quantitative importance, these phenomena appear to originate by the hydrolysis of the Pro4–Gln5 bond, followed by C-terminal sequential degradation of the Arg1–Pro4 tetrapeptide; by the hydrolysis of or Phe7–Phe8 bond (or, possibly, of Gln6–Phe7) leading to release of free Phe and Gln; by hydrolysis of the Gly9–Leu10 bond with subsequent release of Met and Leu. Results obtained appear to be compatible with the expression by SaOS-2 cells
of enzymes already known to catalyze substance P hydrolysis, together with an apparent low efficiency of aminopeptidases.
Because of the activity of C-terminal fragments on NK1 receptors, the delay between primary hydrolysis of substance P and
secondary hydrolysis of its peptidic fragments indicated by the data shown implies a possible persistence of substance P physiological
effects even after degradation of the intact peptide. 相似文献
992.
Rossi C Porcelloni M D'Andrea P Fincham CI Ettorre A Mauro S Squarcia A Bigioni M Parlani M Nardelli F Binaschi M Maggi CA Fattori D 《Bioorganic & medicinal chemistry letters》2011,21(8):2305-2308
We report here the strategy used in our research group to find a new class of histone deacetylase (HDAC) inhibitors.A series of N-substituted 4-alkylpiperazine and 4-alkylpiperidine hydroxamic acids, corresponding to the basic structure of HDAC inhibitors (zinc binding moiety-linker-capping group) has been designed, prepared, and tested for HDAC inhibition.Linker length and aromatic capping group connection were systematically varied to find the optimal geometric parameters. A new series of submicromolar inhibitors was thus identified, which showed antiproliferative activity on HCT-116 colon carcinoma cells. 相似文献
993.
Vicinanza M Di Campli A Polishchuk E Santoro M Di Tullio G Godi A Levtchenko E De Leo MG Polishchuk R Sandoval L Marzolo MP De Matteis MA 《The EMBO journal》2011,30(24):4970-4985
Mutations in the phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P(2)) 5-phosphatase OCRL cause Lowe syndrome, which is characterised by congenital cataracts, central hypotonia, and renal proximal tubular dysfunction. Previous studies have shown that OCRL interacts with components of the endosomal machinery; however, its role in endocytosis, and thus the pathogenic mechanisms of Lowe syndrome, have remained elusive. Here, we show that via its 5-phosphatase activity, OCRL controls early endosome (EE) function. OCRL depletion impairs the recycling of multiple classes of receptors, including megalin (which mediates protein reabsorption in the kidney) that are retained in engorged EEs. These trafficking defects are caused by ectopic accumulation of PtdIns4,5P(2) in EEs, which in turn induces an N-WASP-dependent increase in endosomal F-actin. Our data provide a molecular explanation for renal proximal tubular dysfunction in Lowe syndrome and highlight that tight control of PtdIns4,5P(2) and F-actin at the EEs is essential for exporting cargoes that transit this compartment. 相似文献
994.
The inducible COX-2 enzyme is over-expressed in human breast cancer and its over-expression generally correlates with angiogenesis, deregulation of apoptosis and worse prognosis. This observation may explain the beneficial effect of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors on breast cancer treatment. Here, we evaluated the antiproliferative activity of celecoxib, a selective COX-2 inhibitor, and its nitro-oxy derivative on human breast cancer cells characterized by low and high COX-2 expression, respectively. In ERα(+) MCF-7 cells celecoxib and its derivative induce a strong inhibition of cell growth, inhibition that is associated with the reduction of ERα expression and activation. These effects may be directly associated with ERK and Akt suppression and with PP2A and PTEN induction. In this cell line the drugs exert only weak effect on COX-2 level while they are able to reduce aromatase expression. On the contrary, in ERα(-) MDA-MB-231 cells, both drugs induce a marked inhibition of COX-2, inhibition that is associated with the reduction of aromatase expression and of cell proliferation. In both cell lines the effects of the drugs are associated with the suppression of cell invasion. 相似文献
995.
996.
Arbuscular mycorrhizas (AM) are widespread, ancient endosymbiotic associations that contribute significantly to soil nutrient uptake in plants. We have previously shown that initial fungal penetration of the host root is mediated via a specialized cytoplasmic assembly called the prepenetration apparatus (PPA), which directs AM hyphae through the epidermis (Genre et al., 2005). In vivo confocal microscopy studies performed on Medicago truncatula and Daucus carota, host plants with different patterns of AM colonization, now reveal that subsequent intracellular growth across the root outer cortex is also PPA dependent. On the other hand, inner root cortical colonization leading to arbuscule development involves more varied and complex PPA-related mechanisms. In particular, a striking alignment of polarized PPAs can be observed in adjacent inner cortical cells of D. carota, correlating with the intracellular root colonization strategy of this plant. Ultrastructural analysis of these PPA-containing cells reveals intense membrane trafficking coupled with nuclear enlargement and remodeling, typical features of arbusculated cells. Taken together, these findings imply that prepenetration responses are both conserved and modulated throughout the AM symbiosis as a function of the different stages of fungal accommodation and the host-specific pattern of root colonization. We propose a model for intracellular AM fungal accommodation integrating peri-arbuscular interface formation and the regulation of functional arbuscule development. 相似文献
997.
A Chiechi C Mueller KM Boehm A Romano MS Benassi P Picci LA Liotta V Espina 《BioTechniques》2012,(0):1-7
Members of the heat shock protein-90 (Hsp90) family are key regulators of biological processes through dynamic interaction with a multitude of protein partners. However, the transient nature of these interactions hinders the identification of Hsp90 interactors. Here we show that chemical cross-linking with ethylene glycolbis (succinimidylsuccinate), but not shorter cross-linkers, generated an abundant 240-kDa heteroconjugate of the molecular chaperone Hsp90 in different cell types. The combined use of pharmacological and genetic approaches allowed the characterization of the subunit composition and subcellular compartmentalization of the multimeric protein complex, termed p240. The in situ formation of p240 did not require the N-terminal domain or the ATPase activity of Hsp90. Utilizing subcellular fractionation techniques and a cell-impermeant cross-linker, subpopulations of p240 were found to be present in both the plasma membrane and the mitochondria. The Hsp90-interacting proteins, including Hsp70, p60Hop and the scaffolding protein filamin A, had no role in governing the formation of p240. Therefore, chemical cross-linking combined with proteomic methods has the potential to unravel the protein components of this p240 complex and, more importantly, may provide an approach to expand the range of tools available to the study of the Hsp90 interactome. 相似文献
998.
Fulvia Roletto Arturo P. Galvani Cinzia Cristiani Barbara Valsasina Antonella Landonio Federico Bertolero 《Journal of cellular physiology》1996,166(1):105-111
Basic fibroblast growth factor (bFGF) together with other pleiotropic factors plays an important role in many complex physiological processes such as embryonic development, angiogenesis, and wound repair. Among these factors, hepatocyte growth factor/scatter factor (HGF/SF) which is secreted by cells of mesodermal origin exerts its mito- and motogenic activities on cells of epithelial and endothelial origin. Knowledge of the regulatory mechanisms of HGF/SF may contribute to the understanding of its role in physio-pathological processes. We observed that the secretion of HGF/SF by MRC-5 cells and by other fibroblast-derived cell cultures in conditioned media was enhanced by exposure to bFGF. HGF/SF was measured by the scatter assay, a bioassay for cell motility, and was further characterized by Western blot analysis with anti-HGF/SF antibodies. Exposure of MRC-5 cultures to 10 ng/ml of bFGF resulted already 6 h posttreatment in a threefold higher amount of scatter factor secreted into the medium as compared to untreated cultures. HGF/SF secretion was sustained after bFGF treatment for the following 72 h when increased amounts of HGF/SF were detected both in conditioned media as well as associated to the extracellular matrix. The secretion of HGF/SF in cell supernatants increased dose dependently upon treatment with bFGF starting from basal levels of 6 U/ml and reaching 27 U/ml at 30 ng/ml bFGF, plateauing thereafter. Upregulation of HGF/SF by IL-1, already described by others, was confirmed in this study. Based on our findings an articulated interaction can be speculated for bFGF, HGF/SF, and IL-1, e.g., in tissue regeneration during inflammatory processes or in wound healing. © 1996 Wiley-Liss, Inc. 相似文献
999.
T and B cell responses to cytomegalovirus antigens in healthy blood donors and bone marrow transplant recipients 总被引:1,自引:0,他引:1
Francesco Lolli Vivi-Anne Sundqvist Antonella Castagna Per Ljungman Annika Linde Gudrun Andersson Tomas Olsson Britta Wahren 《FEMS immunology and medical microbiology》1993,7(1):55-62
Abstract We measured the production of interferon-gamma (IFN-γ) from single T cells and the T cell proliferative response to different cytomegalovirus (CMV) antigens in healthy blood donors and bone marrow transplant recipients. The antigens consisted of a CMV nuclear antigen (CMV na) containing the pp65-kDa matrix protein and the immediate early antigens but lacking CMV glycoproteins, and an antigen comprising native CMV glycoproteins (CMV gp). We also measured the IgG antibodies to CMV na and CMV gp. The T cells reacted to CMV na in CMV seropositive blood donors both with the production of IFN-γ and with proliferation, while bone marrow transplant recipients had a deficient T cell response. After stimulation with CMV gp, no T cell response could be observed in CMV seropositive subjects. IgG antibodies to CMV na coexisted in plasma with similar levels of antibodies to CMV gp. 相似文献
1000.
Emanuela Lapice Michele Pinelli Elisabetta Pisu Antonella Monticelli Roberto Gambino Gianfranco Pagano Silvia Valsecchi Sergio Cocozza Gabriele Riccardi Olga Vaccaro 《Cardiovascular diabetology》2010,9(1):1-5