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71.
Petropoulou V Garrigue-Antar L Kadler KE 《The Journal of biological chemistry》2005,280(24):22616-22623
Bone morphogenetic protein 1 (BMP-1), which is a tolloid member of the astacin-like family of zinc metalloproteinases, is a highly effective procollagen C-proteinase (PCP) and chordinase. On the other hand, mammalian tolloid like-2 (mTLL-2) does not cleave chordin or procollagen; procollagen is cleaved by mTLL-2 in the presence of high levels of procollagen C-proteinase enhancer-1 (PCPE-1), for reasons that are unknown. We used these differences in activity between BMP-1 and mTLL-2 to narrow in on the domains in BMP-1 that specify PCP and chordinase activity. Using a domain swap approach, we showed that: 1) the metalloproteinase and CUB2 domains of BMP-1 are absolutely required for PCP activity; swaps with either of the corresponding domains in BMP-1 and mTLL-2 did not result in procollagen cleavage and 2) the proteinase domain of mTLL-2 can cleave chordin if coupled to the CUB1 domain of BMP-1. Therefore, the minimal structure for chordinase activity comprises a metalloproteinase domain (either from BMP-1 or from mTLL-2) and the CUB1 domain of BMP-1 (the CUB1 domain of mTLL-2 cannot substitute for the CUB1 domain of BMP-1). We showed that the minimal procollagen C-proteinase (BMP-1 lacking the EGF and CUB3 domain) was enhanced by PCPE-1 but not as well as BMP-1 retaining the CUB3 domain. Further studies showed that PCPE-1 had no effect on the ability of BMP-1 to cleave chordin. The data support a previously suggested mechanism of PCPE-1 whereby PCPE-1 interacts with procollagen, but in addition, the CUB3 domain of BMP-1 appears to augment the interaction. 相似文献
72.
Anesti V McDonald IR Ramaswamy M Wade WG Kelly DP Wood AP 《Environmental microbiology》2005,7(8):1227-1238
Diverse methylotrophic bacteria were isolated from the tongue, and supra- and subgingival plaque in the mouths of volunteers and patients with periodontitis. One-carbon compounds such as dimethylsulfide in the mouth are likely to be used as growth substrates for these organisms. Methylotrophic strains of Bacillus, Brevibacterium casei, Hyphomicrobium sulfonivorans, Methylobacterium, Micrococcus luteus and Variovorax paradoxus were characterized physiologically and by their 16S rRNA gene sequences. The type strain of B. casei was shown to be methylotrophic. Enzymes of methylotrophic metabolism were characterized in some strains, and activities consistent with growth using known pathways of C1-compound metabolism demonstrated. Genomic DNA from 18 tongue and dental plaque samples from nine volunteers was amplified by the polymerase chain reaction using primers for the 16S rRNA gene of Methylobacterium and the mxaF gene of methanol dehydrogenase. MxaF was detected in all nine volunteers, and Methylobacterium was detected in seven. Methylotrophic activity is thus a feature of the oral bacterial community. 相似文献
73.
Papandreou V Magiatis P Kalpoutzakis E Skaltsounis AL Harvala C 《Zeitschrift für Naturforschung. C, Journal of biosciences》2002,57(3-4):235-238
A new glycoside of salicylic aldehyde, paeonicluside, was isolated from the roots of the Greek endemic species Paeonia clusii subsp. clusii and identified as alpha-L-arabinopyranosyl-(1-->6)-O-beta-D-glucopyranoside of salicylic aldehyde (1). In addition, one characteristic monoterpene and two monoterpene glycosides were identified as paeoniflorigenone, paeoniflorin and benzoyl paeoniflorin, respectively. The structure of 1 was elucidated on the basis of its spectroscopic data and chemical correlation. It is the first time that a derivative of salicylic aldehyde is isolated from the well-studied Paeonia genus. 相似文献
74.
Stéphanie Cherqui Vasiliki Kalatzis Lionel Forestier Isabelle Poras Corinne Antignac 《BMC genomics》2000,1(1):2-5
Background
Cystinosis is an autosomal recessive disorder characterised by an intralysosomal accumulation of cystine, and affected individuals progress to end-stage renal failure before the age of ten. The causative gene, CTNS, was cloned in 1998 and the encoded protein, cystinosin, was predicted to be a lysosomal membrane protein. 相似文献75.
Paola Cipriani Paola Di Benedetto Piero Ruscitti Daniela Verzella Mariafausta Fischietti Francesca Zazzeroni Vasiliki Liakouli Francesco Carubbi Onorina Berardicurti Edoardo Alesse Roberto Giacomelli 《Arthritis research & therapy》2015,17(1)
IntroductionSystemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-β) and endothelin-1 (ET-1) play a major role. In this paper we show that TGF-β and ET-1 receptors co-operate in myofibroblast activation, and macitentan, an ET-1 receptor antagonist binding ET-1 receptors, might interfere with both TGF-β and ET-1 pathways, preventing myofibroblast differentiation.MethodsFibroblasts isolated from healthy controls and SSc patients were treated with TGF-β and ET-1 and successively analyzed for alpha smooth muscle actin (α-SMA) and collagen (Col1A1) expression and for the Sma and Mad Related (SMAD) phosphorylation. We further tested the ability of macitentan to interfere with these process. Furthermore, we silenced ET-1 and endothelin-1 receptor A expression and evaluated the formation of an ET-1/TGF-β receptor complex by immunoprecitation assay.ResultsWe showed myofibroblast activation in SSc fibroblasts assessing the expression of α-SMA and Col1A1, after stimulation with TGF-β and ET-1. Macitentan interfered with both ET-1- and TGF-β-induced fibroblast activation. To explain this unexpected inhibitory effect of macitentan on TGF-β activity, we silenced ET-1 expression on SSc fibroblasts and co-immunoprecipitated these two receptors, showing the formation of an ET-1/TGF-β receptor complex.ConclusionsDuring SSc, ET-1 produced by activated endothelia contributes to myofibroblast activation using TGF-β machinery via an ET-1/TGF-β receptor complex. Macitentan interferes with the profibrotic action of TGF-β, blocking the ET-1 receptor portion of the ET-1/TGF-β receptor complex. 相似文献
76.
A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration
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Vasiliki Maria Rogkoti Franziska Baenke Vincent C de Boer Christian Frezza Almut Schulze Eytan Ruppin 《Molecular systems biology》2014,10(8)
Over the last decade, the field of cancer metabolism has mainly focused on studying the role of tumorigenic metabolic rewiring in supporting cancer proliferation. Here, we perform the first genome‐scale computational study of the metabolic underpinnings of cancer migration. We build genome‐scale metabolic models of the NCI‐60 cell lines that capture the Warburg effect (aerobic glycolysis) typically occurring in cancer cells. The extent of the Warburg effect in each of these cell line models is quantified by the ratio of glycolytic to oxidative ATP flux (AFR), which is found to be highly positively associated with cancer cell migration. We hence predicted that targeting genes that mitigate the Warburg effect by reducing the AFR may specifically inhibit cancer migration. By testing the anti‐migratory effects of silencing such 17 top predicted genes in four breast and lung cancer cell lines, we find that up to 13 of these novel predictions significantly attenuate cell migration either in all or one cell line only, while having almost no effect on cell proliferation. Furthermore, in accordance with the predictions, a significant reduction is observed in the ratio between experimentally measured ECAR and OCR levels following these perturbations. Inhibiting anti‐migratory targets is a promising future avenue in treating cancer since it may decrease cytotoxic‐related side effects that plague current anti‐proliferative treatments. Furthermore, it may reduce cytotoxic‐related clonal selection of more aggressive cancer cells and the likelihood of emerging resistance. 相似文献
77.
Markou A Tsiama V Tournis S Papanastasiou L Tsiavos V Dassou A Vlachou V Papaliodi E Asimaki N Zografos G Piaditis G 《Endocrine practice》2011,17(6):e144-e148
ObjectiveTo present an unusual case of coexisting tumor-induced osteomalacia (TIO) and primary hyperparathyroidism (PHPT).MethodsWe report the clinical features, imaging studies, and the results of laboratory investigations before and after surgical resection of both a soft-tissue tumor and a parathyroid adenoma.ResultsA 44-year-old woman was referred to the endocrinology department with a diagnosis of PHPT accompanied by unusually severe hypophosphatemia, despite having received treatment with cinacalcet. Debilitating muscle weakness and bone pain, severe phosphaturia and hypophosphatemia, inappropriately normal calcitriol, and elevated fibroblast growth factor-23 and intact parathyroid hormone levels raised the suspicion of coexisting TIO and PHPT. Imaging studies were negative, but histologic characteristics of a palpable subcutaneous mass from the patient’s thigh revealed a phosphaturic mesenchymal tumor. Complete remission after surgical removal of both the soft-tissue tumor and the parathyroid adenoma confirmed the diagnosis.ConclusionThe coexistence of TIO and PHPT has not been described before and can cause life-threatening hypophosphatemia. Diagnosis and localization of the tumor is of paramount importance since surgery is the treatment of choice for both TIO and PHPT. (Endocr Pract. 2011;17:e144-e148) 相似文献
78.
Roubelakis MG Bitsika V Zagoura D Trohatou O Pappa KI Makridakis M Antsaklis A Vlahou A Anagnou NP 《Journal of cellular and molecular medicine》2011,15(9):1896-1913
Human mesenchymal progenitor cells (MPCs) are considered to be of great promise for use in tissue repair and regenerative medicine. MPCs represent multipotent adherent cells, able to give rise to multiple mesenchymal lineages such as osteoblasts, adipocytes or chondrocytes. Recently, we identified and characterized human second trimester amniotic fluid (AF) as a novel source of MPCs. Herein, we found that early colonies of AF-MPCs consisted of two morphologically distinct adherent cell types, termed as spindle-shaped (SS) and round-shaped (RS). A detailed analysis of these two populations showed that SS-AF-MPCs expressed CD90 antigen in a higher level and exhibited a greater proliferation and differentiation potential. To characterize better the molecular identity of these two populations, we have generated a comparative proteomic map of SS-AF-MPCs and RS-AF-MPCs, identifying 25 differentially expressed proteins and 10 proteins uniquely expressed in RS-AF-MPCs. Furthermore, SS-AF-MPCs exhibited significantly higher migration ability on extracellular matrices, such as fibronectin and laminin in vitro, compared to RS-AF-MPCs and thus we further evaluated SS-AF-MPCs for potential use as therapeutic tools in vivo. Therefore, we tested whether GFP-lentiviral transduced SS-AF-MPCs retained their stem cell identity, proliferation and differentiation potential. GFP-SS-AF-MPCs were then successfully delivered into immunosuppressed mice, distributed in different tissues and survived longterm in vivo. In summary, these results demonstrated that AF-MPCs consisted of at least two different MPC populations. In addition, SS-AF-MPCs, isolated based on their colony morphology and CD90 expression, represented the only MPC population that can be expanded easily in culture and used as an efficient tool for future in vivo therapeutic applications. 相似文献
79.
Dedmer B Van de Waal Jolanda MH Verspagen Jan F Finke Vasiliki Vournazou Anne K Immers W Edwin A Kardinaal Linda Tonk Sven Becker Ellen Van Donk Petra M Visser Jef Huisman 《The ISME journal》2011,5(9):1438-1450
Climate change scenarios predict a doubling of the atmospheric CO2 concentration by the end of this century. Yet, how rising CO2 will affect the species composition of aquatic microbial communities is still largely an open question. In this study, we develop a resource competition model to investigate competition for dissolved inorganic carbon in dense algal blooms. The model predicts how dynamic changes in carbon chemistry, pH and light conditions during bloom development feed back on competing phytoplankton species. We test the model predictions in chemostat experiments with monocultures and mixtures of a toxic and non-toxic strain of the freshwater cyanobacterium Microcystis aeruginosa. The toxic strain was able to reduce dissolved CO2 to lower concentrations than the non-toxic strain, and became dominant in competition at low CO2 levels. Conversely, the non-toxic strain could grow at lower light levels, and became dominant in competition at high CO2 levels but low light availability. The model captured the observed reversal in competitive dominance, and was quantitatively in good agreement with the results of the competition experiments. To assess whether microcystins might have a role in this reversal of competitive dominance, we performed further competition experiments with the wild-type strain M. aeruginosa PCC 7806 and its mcyB mutant impaired in microcystin production. The microcystin-producing wild type had a strong selective advantage at low CO2 levels but not at high CO2 levels. Our results thus demonstrate both in theory and experiment that rising CO2 levels can alter the community composition and toxicity of harmful algal blooms. 相似文献
80.
Allali S Muller JB Brauner R Lourenço D Boudjenah R Karageorgou V Trivin C Lottmann H Lortat-Jacob S Nihoul-Fékété C De Dreuzy O McElreavey K Bashamboo A 《PloS one》2011,6(10):e24117