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991.
992.
Yuko Arie Masumi Iketani Ken Takamatsu Yoshio Goshima 《Biochemical and biophysical research communications》2009,379(1):11-3034
Intracellular calcium ions (Ca2+) have an essential role in the regulation of neurite outgrowth, but how outgrowth is controlled remains largely unknown. In this study, we examined how the mechanisms of neurite outgrowth change during development in chick and mouse dorsal root ganglion neurons. 2APB, a potent inhibitor of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), inhibited neurite outgrowth at early developmental stages, but not at later stages. In contrast, pharmacological inhibition with Ni2+, Cd2+, or dantrolene revealed that ryanodine receptor (RyR)-mediated Ca2+-induced Ca2+ release (CICR) was involved in neurite outgrowth at later stage, but not at early stages. The distribution of IP3R and RyR in growth cones also changed during development. Furthermore, pharmacological inhibition of the Ca2+-calmodulin-dependent phosphatase calcineurin with FK506 reduced neurite outgrowth only at early stages. These data suggest that the calcium signaling that regulates neurite outgrowth may change during development from an IP3R-mediated pathway to a RyR-mediated pathway. 相似文献
993.
Keita Miyata Tomonori Suzuki Ken Inui Toshihiro Watanabe 《Biochemical and biophysical research communications》2009,384(1):126-130
Clostridium botulinum produces botulinum neurotoxin (BoNT) as a large toxin complex associated with nontoxic-nonhemagglutinin (NTNHA) and/or hemagglutinin components. In the present study, high-level expression of full-length (1197 amino acids) rNTNHA from C. botulinum serotype D strain 4947 (D-4947) was achieved in an Escherichia coli system. Spontaneous nicking of the rNTNHA at a specific site was observed during long-term incubation in the presence of protease inhibitors; this was also observed in natural NTNHA. The rNTNHA assembled with isolated D-4947 BoNT with molar ratio 1:1 to form a toxin complex. The reconstituted toxin complex exhibited dramatic resistance to proteolysis by pepsin or trypsin at high concentrations, despite the fact that the isolated BoNT and rNTNHA proteins were both easily degraded. We provide definitive evidence that NTNHA plays a crucial role in protecting BoNT, which is an oral toxin, from digestion by proteases common in the stomach and intestine. 相似文献
994.
Martin S Cosset EC Terrand J Maglott A Takeda K Dontenwill M 《Biochimica et biophysica acta》2009,1793(2):354-367
Caveolin-1 plays a checkpoint function in the regulation of processes often altered in cancer. Although increased expression of caveolin-1 seems to be the norm in the glioma family of malignancies, populations of caveolin-1 positive and negative cells coexist among glioblastoma specimens. As no data are available to date on the contribution of such cells to the phenotype of glioblastoma, we manipulated caveolin-1 in the glioblastoma cell line U87MG. We showed that caveolin-1 plays a critical role in the aggressiveness of glioblastoma. We identified integrins as the main set of genes affected by caveolin-1. We reported here that the phenotypic changes observed after caveolin-1 modulation were mediated by alpha(5)beta(1) integrins. As a consequence of the regulation of alpha(5)beta(1) levels by caveolin-1, the sensitivity of cells to the specific alpha(5)beta(1) integrin antagonist, SJ749, was affected. Mediator of caveolin-1 effects, alpha(5)beta(1) integrin, is also a marker for glioma aggressiveness and an efficient target for the treatment of glioma especially the ones exerting the highest aggressive phenotype. 相似文献
995.
Shane Massey Abhay H. Pande Michael Taylor Ken Teter 《Journal of molecular biology》2009,393(5):1083-1096
Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER) by retrograde vesicular transport. The catalytic subunit of CT (CTA1) then crosses the ER membrane and enters the cytosol in a process that involves the quality control mechanism of ER-associated degradation. The molecular details of this dislocation event have not been fully characterized. Here, we report that thermal instability in the CTA1 subunit—specifically, the loss of CTA1 tertiary structure at 37 °C—triggers toxin dislocation. Biophysical studies found that glycerol preferentially stabilized the tertiary structure of CTA1 without having any noticeable effect on the thermal stability of its secondary structure. The thermal disordering of CTA1 tertiary structure normally preceded the perturbation of its secondary structure, but in the presence of 10% glycerol the temperature-induced loss of CTA1 tertiary structure occurred at higher temperatures in tandem with the loss of CTA1 secondary structure. The glycerol-induced stabilization of CTA1 tertiary structure blocked CTA1 dislocation from the ER and instead promoted CTA1 secretion into the extracellular medium. This, in turn, inhibited CT intoxication. Glycerol treatment also inhibited the in vitro degradation of CTA1 by the core 20S proteasome. Collectively, these findings indicate that toxin thermal instability plays a key role in the intoxication process. They also suggest the stabilization of CTA1 tertiary structure is a potential goal for novel antitoxin therapeutic agents. 相似文献
996.
Yukari Suzuki Michiko Minami Miho Suzuki Keiko Abe Shuhei Zenno Masafumi Tsujimoto Ken Matsumoto Yasufumi Minami 《The Journal of biological chemistry》2009,284(51):35597-35604
The eukaryotic translation initiation factor eIF4E plays a critical role in the control of translation initiation through binding to the mRNA 5′ cap structure. eIF4E is also a component of processing bodies and stress granules, which are two types of cytoplasmic RNA granule in which translationally inactivated mRNAs accumulate. We found that treatment with the Hsp90 inhibitor geldanamycin leads to a substantial reduction in the number of HeLa cells that contain processing bodies. In contrast, stress granules are not disrupted but seem to be only partially affected by the inhibition of Hsp90. However, it is striking that eIF4E as well as its binding partner eIF4E transporter (4E-T), which mediates the import of eIF4E into the nucleus, are obviously lost from stress granules. Furthermore, the amount of eIF4G that is associated with the cap via eIF4E is reduced by geldanamycin treatment. Thus, the chaperone activity of Hsp90 probably contributes to the correct localization of eIF4E and 4E-T to stress granules and also to the interaction between eIF4E and eIF4G, both of which may be needed for eIF4E to acquire the physiological functionality that underlies the mechanism of translation initiation. 相似文献
997.
Oksaharju A Lappalainen J Tuomainen AM Pussinen PJ Puolakkainen M Kovanen PT Lindstedt KA 《Journal of cellular and molecular medicine》2009,13(1):103-113
A broad variety of microbes are present in atherosclerotic plaques and chronic bacterial infection increases the risk of atherosclerosis by mechanisms that have remained vague. One possible mechanism is that bacteria or bacterial products activate plaque mast cells that are known to participate in the pathogenesis of atherosclerosis. Here, we show by real-time PCR analysis and ELISA that Chlamydia pneumoniae (Cpn) and a periodontal pathogen, Aggregatibacter actinomycetemcomitans (Aa), both induce a time and concentration-dependent expression and secretion of interleukin 8 (IL-8), tumour necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) by cultured human peripheral blood-derived mast cells, but not anti-inflammatory molecules, such as IL-10 or transforming growth factor β1 (TGF-β1). The IL-8 and MCP-1 responses were immediate, whereas the onset of TNF-α secretion was delayed. The Cpn-mediated pro-inflammatory effect was attenuated when the bacteria were inactivated by UV-treatment. Human monocyte-derived macrophages that were pre-infected with Cpn also induced a significant pro-inflammatory response in human mast cells, both in cocultures and when preconditioned media from Cpn-infected macrophages were used. Intranasal and intravenous administration of live Cpn and Aa, respectively induced an accumulation of activated mast cells in the aortic sinus of apolipoprotein E-deficient mice, however, with varying responses in the systemic levels of lipopolysaccharide (LPS) and TNF-α. Pro-atherogenic Cpn and Aa induce a pro-inflammatory response in cultured human connective tissue-type mast cells and activation of mouse aortic mast cells in vivo . 相似文献
998.
Dispersal failure contributes to plant losses in NW Europe 总被引:1,自引:0,他引:1
Wim A. Ozinga Christine Römermann Renée M. Bekker reas Prinzing Wil L. M. Tamis Joop H. J. Schaminée Stephan M. Hennekens Ken Thompson Peter Poschlod Michael Kleyer Jan P. Bakker Jan M. van Groenendael 《Ecology letters》2009,12(1):66-74
The ongoing decline of many plant species in Northwest Europe indicates that traditional conservation measures to improve the habitat quality, although useful, are not enough to halt diversity losses. Using recent databases, we show for the first time that differences between species in adaptations to various dispersal vectors, in combination with changes in the availability of these vectors, contribute significantly to explaining losses in plant diversity in Northwest Europe in the 20th century. Species with water- or fur-assisted dispersal are over-represented among declining species, while others (wind- or bird-assisted dispersal) are under-represented. Our analysis indicates that the 'colonization deficit' due to a degraded dispersal infrastructure is no less important in explaining plant diversity losses than the more commonly accepted effect of eutrophication and associated niche-based processes. Our findings call for measures that aim to restore the dispersal infrastructure across entire regions and that go beyond current conservation practices. 相似文献
999.
Erin Stewart Lindquist Ken W. Krauss Peter T. Green Dennis J. O'Dowd Peter M. Sherman and Thomas J. Smith III 《Biological reviews of the Cambridge Philosophical Society》2009,84(2):203-223
Plant populations are regulated by a diverse assortment of abiotic and biotic factors that influence seed dispersal and viability, and seedling establishment and growth at the microsite. Rarely does one animal guild exert as significant an influence on different plant assemblages as land crabs. We review three tropical coastal ecosystems–mangroves, island maritime forests, and mainland coastal terrestrial forests–where land crabs directly influence forest composition by limiting tree establishment and recruitment. Land crabs differentially prey on seeds, propagules and seedlings along nutrient, chemical and physical environmental gradients. In all of these ecosystems, but especially mangroves, abiotic gradients are well studied, strong and influence plant species distributions. However, we suggest that crab predation has primacy over many of these environmental factors by acting as the first limiting factor of tropical tree recruitment to drive the potential structural and compositional organisation of coastal forests. We show that the influence of crabs varies relative to tidal gradient, shoreline distance, canopy position, time, season, tree species and fruiting periodicity. Crabs also facilitate forest growth and development through such activities as excavation of burrows, creation of soil mounds, aeration of soils, removal of leaf litter into burrows and creation of carbon-rich soil microhabitats. For all three systems, land crabs influence the distribution, density and size-class structure of tree populations. Indeed, crabs are among the major drivers of tree recruitment in tropical coastal forest ecosystems, and their conservation should be included in management plans of these forests. 相似文献
1000.
Chris M Cirimotich Jaclyn C Scott Aaron T Phillips Brian J Geiss Ken E Olson 《BMC microbiology》2009,9(1):49