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131.
Pol Nadal Jimenez Gudrun Koch Jessica A. Thompson Karina B. Xavier Robbert H. Cool Wim J. Quax 《Microbiology and molecular biology reviews》2012,76(1):46-65
Summary: Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In several pathogens, this process triggers the production of virulence factors and/or a switch in bacterial lifestyle that is a major determining factor in the outcome and severity of the infection. Understanding how bacteria control these signaling systems is crucial to the development of novel antimicrobial agents capable of reducing virulence while allowing the immune system of the host to clear bacterial infection, an approach likely to reduce the selective pressures for development of resistance. We provide here an up-to-date overview of the molecular basis and physiological implications of cell-to-cell signaling systems in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas aeruginosa. All of the known cell-to-cell signaling systems in this bacterium are described, from the most-studied systems, i.e., N-acyl homoserine lactones (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), to less-well-studied signaling molecules, including diketopiperazines, fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and pyocyanin. This overview clearly illustrates that bacterial communication is far more complex than initially thought and delivers a clear distinction between signals that are quorum sensing dependent and those relying on alternative factors for their production. 相似文献
132.
Szegezdi E Reis CR van der Sloot AM Natoni A O'Reilly A Reeve J Cool RH O'Dwyer M Knapper S Serrano L Quax WJ Samali A 《Journal of cellular and molecular medicine》2011,15(10):2216-2231
Despite progress in the treatment of acute myelogenous leukaemia (AML) the outcome often remains poor. Tumour necrosis factor related apoptosis-inducing ligand (TRAIL) is a promising therapeutic agent in many different types of tumours, but AML cells are relatively insensitive to TRAIL-induced apoptosis. Here we show that TRAIL-induced apoptosis in AML cells is predominantly mediated by death receptor 4 (DR4) and not DR5. Therefore, we constructed a variant of TRAIL (rhTRAIL-C3) that is a strong inducer of DR4-mediated apoptosis. TRAIL-C3 demonstrated much stronger pro-apoptotic activity than wild-type (WT) TRAIL in a panel of AML cell lines as well as in primary AML blasts. The higher pro-apoptotic potential was further enhanced when the TRAIL mutant was used in combination with BMS-345541, a selective inhibitor of inhibitor-κB kinases. It illustrates that combination of this TRAIL variant with chemotherapeutics or other targeted agents can kill AML with high efficacy. This may represent a major advantage over the currently used therapies that have serious toxic side effects. The high efficacy of rhTRAIL-C3 containing therapies may enable the use of lower drug doses to reduce the toxic side effects and improve patient outcome. Our findings suggest that the rational design of TRAIL variants that target DR4 potentiate the death-inducing activity of TRAIL and offer a novel therapeutic strategy for the treatment of AML. 相似文献
133.
Stanley CK Cheung Li-zhong Liu Lin-lin Lan Qiao-quan Liu Samuel SM Sun Juliana CN Chan Peter CY Tong 《BMC biotechnology》2011,11(1):37
Background
Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains. 相似文献134.
Yan D Chen D Cool SM van Wijnen AJ Mikecz K Murphy G Im HJ 《Arthritis research & therapy》2011,13(4):R130-13
Introduction
Cartilage degeneration driven by catabolic stimuli is a critical pathophysiological process in osteoarthritis (OA). We have defined fibroblast growth factor 2 (FGF-2) as a degenerative mediator in adult human articular chondrocytes. Biological effects mediated by FGF-2 include inhibition of proteoglycan production, up-regulation of matrix metalloproteinase-13 (MMP-13), and stimulation of other catabolic factors. In this study, we identified the specific receptor responsible for the catabolic functions of FGF-2, and established a pathophysiological connection between the FGF-2 receptor and OA. 相似文献135.
Carlos R. Reis Aart H. G. van Assen Wim J. Quax Robbert H. Cool 《Molecular & cellular proteomics : MCP》2011,10(1):M110.002808
Characterization of the binding of a tumor necrosis factor (TNF) ligand to its receptor(s) is pivotal to understand how these proteins initiate signal transduction pathways. Unfortunately, kinetic elucidation of these interactions is strongly hampered by the multivalent nature of the binding partners. The interaction between TNF-related apoptosis-inducing ligand and its death receptors was analyzed using in-depth applications of surface plasmon resonance technology. Variations in receptor density and sensor chip type allowed us to manipulate the stoichiometry of the formed complex, and the rate constants describing the binding of trimeric TNF-related apoptosis-inducing ligand to only one receptor molecule were determined. Remarkably, the affinity of this trimer-monomer complex is in the picomolar range, and its dissociation very slow. Further analysis showed that the second and third receptor molecules bind with lower affinity to the preformed trimer-monomer complex. This together with results obtained with receptor activator of NF-κB ligand and B cell-activating factor strongly suggests that the binding of TNF family ligands to their receptors is initiated via the formation of a trimer-monomer complex that is sufficiently stable to allow binding of two additional receptor molecules. These results suggest that avidity does not play a significant role and thus provide new insight in how TNF ligands form the biologically important complexes with their receptors.Cytokines are signaling molecules involved in a range of biological processes and diseases. Cytokines and receptors belonging to the TNF superfamily have been a subject of interest for developing novel therapies for numerous diseases (1). These cytokines e.g. TNFα, TRAIL,1 RANKL, and BAFF are type II transmembrane proteins, and the extracellular C-terminal moiety can be released by specific proteases to form a soluble and active protein consisting of three subunits of each ∼20 kDa (2). As one of the most promising anticancer therapeutic candidates, recombinant human TRAIL (rhTRAIL; comprising amino acids 114–281) is able to kill a variety of cancer cells but not healthy cells. Currently, rhTRAIL is being tested in clinical phase II studies as an anticancer biopharmaceutical (3).Despite good progress on structural insight, analysis of the interactions between TNF ligand family members and their receptors lacks unambiguous results. This seems mainly caused by the multivalent character of these molecules, i.e. trimeric cytokines but also often dimeric receptor-Fc fusions, which lead to complex kinetic behavior. In a series of experiments, we obtained several indications that surface plasmon resonance (SPR) assays with rhTRAIL WT and receptor-specific variants (4–6) offer opportunities to establish a better characterization of their interactions with receptor molecules. For this, we meticulously applied SPR technology to elucidate the dynamics of complex formation of this important group of cytokines. We used rhTRAIL WT; a DR5-specific mutant, rhTRAILD269H/E195R; and death receptors DR4 and DR5 to develop the method, but we show with examples of other members of the TNF family that the method is generally applicable. Apart from presenting a method allowing unambiguous affinity determination, our results demonstrate that the binding mechanism of these cytokines is initiated via a high affinity interaction with the first receptor molecule, bringing the cytokine to the membrane. 相似文献
136.
137.
Koen Breyne Steven K. Cool Dieter Demon Kristel Demeyere Tom Vandenberghe Peter Vandenabeele Harald Carlsen Wim Van Den Broeck Niek N. Sanders Evelyne Meyer 《PloS one》2014,9(8)
Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1. 相似文献
138.
Margaretha van der Deen Hanna Taipaleenm?ki Ying Zhang Nadiya M. Teplyuk Anurag Gupta Senthilkumar Cinghu Kristen Shogren Avudaiappan Maran Michael J. Yaszemski Ling Ling Simon M. Cool David T. Leong Christian Dierkes Jozef Zustin Manuel Salto-Tellez Yoshiaki Ito Suk-Chul Bae Maria Zielenska Jeremy A. Squire Jane B. Lian Janet L. Stein Gerard P. Zambetti Stephen N. Jones Mario Galindo Eric Hesse Gary S. Stein Andre J. van Wijnen 《The Journal of biological chemistry》2013,288(29):21307-21319
139.
A novel approach to the design of sensitive fluorescent probes for nucleic acids detection is proposed. Suitable modifications of tri- and pentamethine cyanine dyes in the polymethine chain and/or in the heterocyclic residues can result in a significant decrease in unbound dye fluorescence intensity and an increase in dye emission intensity in the presence of DNA compared to the unsubstituted dye. The sharp enhancement in the fluorescence intensity upon dye interaction with double-stranded DNA permits the application of the modified tri- and pentamethine dyes as fluorescent probes in double-stranded DNA detection in homogeneous assays. 相似文献
140.
SM Jeyakumar M Raja Gopal Reddy C Garlapati S Desi Reddy A Vajreswari 《Biochemistry and Biophysics Reports》2020
The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status. 相似文献