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41.
Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway 总被引:5,自引:0,他引:5
An important step in retinal development is the positioning of progenitors within the eye field where they receive the local environmental signals that will direct their ultimate fate. Recent evidence indicates that ephrinB1 functions in retinal progenitor movement, but the signalling pathway is unclear. We present evidence that ephrinB1 signals through its intracellular domain to control retinal progenitor movement into the eye field by interacting with Xenopus Dishevelled (Xdsh), and by using the planar cell polarity (PCP) pathway. Blocking Xdsh translation prevents retinal progeny from entering the eye field, similarly to the morpholino-mediated loss of ephrinB1 (ref. 2). Overexpression of Xdsh can rescue the phenotype induced by loss of ephrinB1, and this rescue (as well as a physical association between Xdsh and ephrinB1) is completely dependent on the DEP (Dishevelled, Egl-10, Pleckstrin) domain of Xdsh. Similar gain- and loss-of-function experiments suggest that Xdsh associates with ephrinB1 and mediates ephrinB1 signalling through downstream members of the PCP pathway during eye field formation. 相似文献
42.
Forns P Esteve C Taboada L Alonso JA Orellana A Maldonado M Carreño C Ramis I López M Miralpeix M Vidal B 《Bioorganic & medicinal chemistry letters》2012,22(8):2784-2788
A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay. 相似文献
43.
Luisa Diomede Cristina Soria Margherita Romeo Sofia Giorgetti Loredana Marchese Patrizia Palma Mangione Riccardo Porcari Irene Zorzoli Mario Salmona Vittorio Bellotti Monica Stoppini 《PloS one》2012,7(12)
Availability of living organisms to mimic key step of amyloidogenesis of human protein has become an indispensable tool for our translation approach aiming at filling the deep gap existing between the biophysical and biochemical data obtained in vitro and the pathological features observed in patients. Human β2-microglobulin (β2-m) causes systemic amyloidosis in haemodialysed patients. The structure, misfolding propensity, kinetics of fibrillogenesis and cytotoxicity of this protein, in vitro, have been studied more extensively than for any other globular protein. However, no suitable animal model for β2-m amyloidosis has been so far reported. We have now established and characterized three new transgenic C. elegans strains expressing wild type human β2-m and two highly amyloidogenic isoforms: P32G variant and the truncated form ΔN6 lacking of the 6 N-terminal residues. The expression of human β2-m affects the larval growth of C. elegans and the severity of the damage correlates with the intrinsic propensity to self-aggregate that has been reported in previous in vitro studies. We have no evidence of the formation of amyloid deposits in the body-wall muscles of worms. However, we discovered a strict correlation between the pathological phenotype and the presence of oligomeric species recognized by the A11 antibody. The strains expressing human β2-m exhibit a locomotory defect quantified with the body bends assay. Here we show that tetracyclines can correct this abnormality confirming that these compounds are able to protect a living organism from the proteotoxicity of human β2-m. 相似文献
44.
Calvanese V Horrillo A Hmadcha A Suarez-Alvarez B Fernandez AF Lara E Casado S Menendez P Bueno C Garcia-Castro J Rubio R Lapunzina P Alaminos M Borghese L Terstegge S Harrison NJ Moore HD Brüstle O Lopez-Larrea C Andrews PW Soria B Esteller M Fraga MF 《PloS one》2008,3(9):e3294
Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation. 相似文献
45.
Arash Rafii Pejman Mirshahi Mary Poupot Anne-Marie Faussat Anne Simon Elodie Ducros Eliane Mery Bettina Couderc Raphael Lis Jerome Capdet Julie Bergalet Denis Querleu Francoise Dagonnet Jean-Jacques Fournié Jean-Pierre Marie Eric Pujade-Lauraine Gilles Favre Jeanine Soria Massoud Mirshahi 《PloS one》2008,3(12)
Background
The microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.Methodology/Principal Findings
We isolated an original type of stromal cells, referred to as “Hospicells” from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.Conclusions/Significance
This is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient''s tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy. 相似文献46.
Woo J Chae YK Jang SJ Kim MS Baek JH Park JC Trink B Ratovitski E Lee T Park B Park M Kang JH Soria JC Lee J Califano J Sidransky D Moon C 《Biochemical and biophysical research communications》2008,366(2):321-327
Phosphorylation pathway has been identified as an important step in membrane trafficking for AQP5. We generated stably transfected BEAS-2B human bronchial epithelial cells with various over-expression constructs on permeable support. In stable cells with wild-type AQP5 and S156A (AQP5 mutant targeting PKA consensus sequence), AQP5 expression was predominantly polarized to the apical membrane, whereas stable cells with N185D (AQP5 mutant targeting second NPA motif), mainly localized to the cytoplasm. Treatment with H89 and/or chlorophenylthio-cAMP (cpt-cAMP) did not affect membrane expression of AQP5 in any of three stable cells. In cells with wild-type AQP5 and N185D, AQP5s were phosphorylated by PKA, while phosphorylation of AQP5 was not detected in cells with S156A. These results indicate that, in AQP5, serine156 may be phosphorylated by PKA, but membrane expression of AQP5 may not be regulated by PKA phosphorylation. We conclude that AQP5 membrane targeting can include more than one mechanism besides cAMP dependent phosphorylation. 相似文献
47.
M A Soria M C Coca Garcia M E Gomez Carretero A Represa Bermejo 《Acta anatomica》1985,124(3-4):173-177
We have studied kidney samples of 16 garden dormouses (Eliomys quercinus L.) divided into two groups, 8 hibernating and 8 non-hibernating. Hibernation produces structural modifications in the glomerular ultrafilter: (1) the endothelial pores decrease in number and size; (2) the podocytic food processes increase in number and the slit pores decrease in size; (3) in the basement membrane there are no structural morphological modifications. In short, we could say that the permeability of the glomerular ultrafilter decreases during hibernation. This fact helps to understand the decrease in the rate of urine formation that takes place in the presence of a low body temperature and a metabolic depression. 相似文献
48.
The fosfomycin resistance protein FosA is a member of a distinct superfamily of metalloenzymes containing glyoxalase I, extradiol dioxygenases, and methylmalonyl-CoA epimerase. The dimeric enzyme, with the aid of a single mononuclear Mn2+ site in each subunit, catalyzes the addition of glutathione (GSH) to the oxirane ring of the antibiotic, rendering it inactive. Sequence alignments suggest that the metal binding site of FosA is composed of three residues: H7, H67, and E113. The single mutants H7A, H67A, and E113A as well as the more conservative mutants H7Q, H67Q, and E113Q exhibit marked decreases in the ability to bind Mn2+ and, in most instances, decreases in catalytic efficiency and the ability to confer resistance to the antibiotic. The enzyme also requires the monovalent cation K+ for optimal activity. The K+ ion activates the enzyme 100-fold with an activation constant of 6 mM, well below the physiologic concentration of K+ in E. coli. K+ can be replaced by other monovalent cations of similar ionic radii. Several lines of evidence suggest that the K+ ion interacts directly with the active site. Interaction of the enzyme with K+ is found to be dependent on the presence of the substrate fosfomycin. Moreover, the E113Q mutant exhibits a kcat which is 40% that of wild-type in the absence of K+. This mutant is not activated by monovalent cations. The behavior of the E113Q mutant is consistent with the proposition that the K+ ion helps balance the charge at the metal center, further lowering the activation barrier for addition of the anionic nucleophile. The fully activated, native enzyme provides a rate acceleration of >10(15) with respect to the spontaneous addition of GSH to the oxirane. 相似文献
49.
J. Soria C. Soria O. Bertrand M. Samama 《Biochemical and biophysical research communications》1978,82(2):442-450
In order to determine the active groups of the fibrinogen molecule in ADP induced aggregation, various cleavage fragments of fibrinogen were tested on plasma protein-free platelets. An original technique is described for the isolation of fibrinogen glycopeptides. The glycopeptides thus obtained exert an inhibition on platelet aggregation by ADP in the presence of fibrinogen, when incubated previously with the plasma protein free platelets. The carbohydrate fraction seems thus to have an important role on ADP platelet aggregation.The N. DSK and E fragments are inactive as cofactors of ADP induced aggregation.It is suggested that the N-terminal part of the Bβ chain does not have an important role in the cofactor activity of fibrinogen. Moreover, the importance of an intact fibrinogen molecule is underlined. 相似文献