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151.
Five bis(3-aryl-6,6-dimethylcyclohexadienyl)ruthenium complexes (4a-4e) are prepared by reactions between di-μ-chlorodichlorobis[(1-3η:6-8η)-2,7-dimethyl-octadienyl]diruthenium and the corresponding dienes. The larger aryl substituents increase the barrier to rotation in 4a-4e relative to bis(3-methyl-6,6-cyclohexadienyl)ruthenium (5b). The activation parameters were determined by line-shape analysis for the exchange process in 4a: ΔG† (183 K), 8.0 ± 0.2 kcal/mol; ΔH†, 10.3 kcal/mol; and ΔS†, 13 cal/mol/K. The electronic effect of the aryl substituents on the cyclohexadienyl ligand on the oxidation potential of the complex are compared to the effect of methyl substituents. 相似文献
152.
Doyle SL Jefferies CA Feighery C O'Neill LA 《The Journal of biological chemistry》2007,282(51):36953-36960
Toll-like receptors (TLRs) are a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. TLR7 and TLR8 sense single-stranded RNA from viruses or host ribonucleoproteins and synthetic imidazoquinolines such as R848, whereas TLR9 senses unmethylated CpG motifs in viral and bacterial DNA and in host DNA. Here we report the endogenous interaction between Brutons's tyrosine kinase (Btk) and human TLR8 and TLR9 in the monocytic cell line THP1. We also show that R848, single-stranded RNA, and CpGB-DNA activate Btk in THP1 cells as shown by phosphorylation of the tyrosine 223 residue of Btk and also by increased autokinase activity. We demonstrate that Btk is required for NFkappaB activation, participating in the pathway to increased phosphorylation of p65 on serine 536 activated by TLR8 and TLR9. Finally we demonstrate that peripheral blood mononuclear cells from patients with X-linked agammaglobulinaemia (XLA) that have dysfunctional Btk are impaired in the induction of interleukin-6 by CpGB-DNA. This study therefore establishes Btk as a key signaling molecule that interacts with and acts downstream of TLR8 and TLR9. Lack of functioning Btk in XLA patients downstream of TLR8 and TLR9 might explain the susceptibility of XLA patients to viral infections. 相似文献
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Endopeptidase 24.15 (ep24.15: EC3.4.24.15), a secreted protein involved in peptide metabolism, is unusual in that it does not contain a signal peptide sequence. In this work, we describe the physical interaction between ep24.15 and 14-3-3 epsilon, one isoform of a family of ubiquitous phosphoserine/threonine-scaffold proteins that organizes cell signaling and is involved in exocytosis. The interaction between ep24.15 and 14-3-3 epsilon increased following phosphorylation of ep24.15 at Ser(644) by protein kinase A (PKA). The co-localization of ep24.15 and 14-3-3 epsilon was increased by exposure of HEK293 cells (human embryonic kidney cells) to forskolin (10 microm). Overexpression of 14-3-3 epsilon in HEK293 cells almost doubled the secretion of ep24.15 stimulated by A23187 (7.5 microm) from 10%[1.4 +/- 0.24 AFU/(min 10(6) cells)] to 19%[2.54 +/- 0.24 AFU/(min 10(6) cells)] (p < 0.001) of the total intracellular enzyme activity. Treatment with forskolin had a synergistic effect on the A23187-stimulated secretion of ep24.15 that was totally blocked by the PKA inhibitor KT5720. The ep24.15 point mutation S644A reduced the co-localization of ep24.15 and 14-3-3 in stably transfected HEK293 cells. Indeed, secretion of the ep24.15 S644A mutant from these cells was only slightly stimulated by A23187 and insensitive to forskolin, in contrast to that of the wild type enzyme. Together, these data suggest that prior interaction with 14-3-3 is an important step in the unconventional stimulated secretion of ep24.15. 相似文献
157.
Bashir M. Mohamed Conleth Feighery Yvonne Williams Anthony Davies Dermot Kelleher Yuri Volkov Jacinta Kelly Mohamed Abuzakouk 《Central European Journal of Biology》2008,3(3):258-267
Coeliac disease is characterised by inflammation of small intestinal mucosa accompanied by abnormal villous architecture.
It is now accepted that some patients with positive coeliac serology tests may have minor mucosal lesions that may not be
apparent on routine histopathological analysis. The aim of the study was to perform detailed examination of enterocyte morphology
and cytoskeletal structures using a high content analysis technology. Duodenal biopsies from 14 untreated and 10 treated coeliac
patients and from 20 non-coeliac controls were examined. Tissue sections from six patients (study group subjects) before and
after the development of gluten-sensitive enteropathy were also investigated. Immunohistochemical studies were performed on
paraffin-embedded sections using an anti-α-tubulin antibody. Significant differences in enterocyte morphology and intracellular
cytoskeletal structures were demonstrated in patients with proven coeliac disease and in the study group subjects. These changes
were present in study group biopsies before evidence of enteropathy, as assessed by routine microscopy. This is the first
study to demonstrate detailed characteristics of enterocyte morphology in coeliac patients using a high content analysis approach.
The use of this technology allows a quantitative analysis of enterocyte intracellular structures from routine biopsy material
and permits detection of subtle changes that precede the characteristic histological lesion. 相似文献
158.
Time-dependent alterations in neural activity have been established during the acquisition and consolidation of a stepdown passive avoidance paradigm. Change in neural activity was established by administering a glucose analogue, [3H]2-deoxyglucose, 50min prior to sacrifice and estimating perchloric acid soluble counts in nine hand dissected brain regions. Change in [3H]2-deoxyglucose uptake was closely paralleled in both trained and yoked animals for up to 40min following task acquisition however the striatum was the only area to exhibit a task-specific increase in [3H]2-deoxyglucose uptake at 20–30min after training. Longterm changes in neural activity were also apparent as the amygdala and brainstem showed increased [3H]2-deoxyglucose uptake at the 24h time point. No further paradigm-specific changes were apparent at 48 h. These findings are concluded to suggest that the striatum is involved in the early events of acquiring a passive avoidance response and the amygdala and brainstem during the later events. 相似文献
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