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排序方式: 共有255条查询结果,搜索用时 62 毫秒
21.
Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy 总被引:8,自引:0,他引:8
Vaya J Mahmood S Goldblum A Aviram M Volkova N Shaalan A Musa R Tamir S 《Phytochemistry》2003,62(1):89-99
Twenty flavonoid compounds of five different subclasses were selected, and the relationship of their structure to the inhibition of low-density lipoprotein (LDL) oxidation in vitro was investigated. The most effective inhibitors, by either copper ion or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) induction, were flavonols and/or flavonoids with two adjacent hydroxyl groups at ring B. In the presence of the later catechol group, the contribution of the double bond and the carbonyl group at ring C was negligible. Isoflavonoids were more effective inhibitors than other flavonoid subclasses with similar structure. Substituting ring B with hydroxyl group(s) at 2' position resulted in a significantly higher inhibitory effect than by substituting ring A or ring B at other positions. The type of LDL inducer had no effect in flavonoids with catechol structure. Calculated heat of formation data (deltadeltaH(f)) revealed that the donation of a hydrogen atom from position 3 was the most likely result, followed by that of a hydroxyl from ring B. Position 3 was favored only in the presence of conjugated double bonds between ring A to ring B. This study makes it possible to assign the contribution of different functional groups among the flavonoid subclasses to in vitro inhibition of LDL oxidation. 相似文献
22.
23.
Altered composition of the immunological synapse in an anergic, age-dependent memory T cell subset 总被引:5,自引:0,他引:5
Eisenbraun MD Tamir A Miller RA 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(12):6105-6112
In young mice, memory CD4 T lymphocytes with high P-glycoprotein activity (P-gp(high)) are unresponsive to TCR stimulation in vitro but can be activated by PMA plus ionomycin. The proportion of these hyporesponsive cells increases considerably with age. The earliest events in T cell activation were studied in P-gp(high) and P-gp(low) CD4 memory cells at the single-cell level using confocal immunofluorescence methods. Recruitment of both linker for activation of T cells (LAT) and protein kinase C-theta to the immunological synapse, i.e., the site of T cell interaction with stimulator cells, was greatly impaired in P-gp(high) cells from both young and old mice. Translocation of NF-AT to the nucleus, CD69 expression, and proliferative capacity were also diminished to a similar extent in P-gp(high) cells under the same activation conditions. In contrast, movement of c-Cbl to the synapse region occurred in a high proportion of CD4 memory T cells regardless of P-gp subset or age. Moreover, although P-gp(low) cells frequently recruited both c-Cbl and LAT to the APC synapse, cells in the less responsive P-gp(high) subset frequently relocated c-Cbl, but not LAT, to the interface region. In some systems, c-Cbl can act as a negative regulator of receptor-dependent tyrosine kinases, and alterations of c-Cbl to LAT ratios in the P-gp(high) subset may thus contribute to the hyporesponsiveness of this age-dependent, anergic memory cell population. 相似文献
24.
Fong DC Brauweiler A Minskoff SA Bruhns P Tamir I Mellman I Daeron M Cambier JC 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(8):4453-4462
The low-affinity receptor for IgG, FcgammaRIIB, functions broadly in the immune system, blocking mast cell degranulation, dampening the humoral immune response, and reducing the risk of autoimmunity. Previous studies concluded that inhibitory signal transduction by FcgammaRIIB is mediated solely by its immunoreceptor tyrosine-based inhibition motif (ITIM) that, when phosphorylated, recruits the SH2-containing inositol 5'- phosphatase SHIP and the SH2-containing tyrosine phosphatases SHP-1 and SHP-2. The mutational analysis reported here reveals that the receptor's C-terminal 16 residues are also required for detectable FcgammaRIIB association with SHIP in vivo and for FcgammaRIIB-mediated phosphatidylinositol 3-kinase hydrolysis by SHIP. Although the ITIM appears to contain all the structural information required for receptor-mediated tyrosine phosphorylation of SHIP, phosphorylation is enhanced when the C-terminal sequence is present. Additionally, FcgammaRIIB-mediated dephosphorylation of CD19 is independent of the cytoplasmic tail distal from residue 237, including the ITIM. Finally, the findings indicate that tyrosines 290, 309, and 326 are all sites of significant FcgammaRIIB1 phosphorylation following coaggregation with B cell Ag receptor. Thus, we conclude that multiple sites in FcgammaRIIB contribute uniquely to transduction of FcgammaRIIB-mediated inhibitory signals. 相似文献
25.
Kristina Kirschner Shamith A. Samarajiwa Jonathan M. Cairns Suraj Menon Pedro A. Pérez-Mancera Kosuke Tomimatsu Camino Bermejo-Rodriguez Yoko Ito Tamir Chandra Masako Narita Scott K. Lyons Andy G. Lynch Hiroshi Kimura Tetsuya Ohbayashi Simon Tavaré Masashi Narita 《PLoS genetics》2015,11(3)
The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage) and chronically activated (in senescent or pro-apoptotic conditions) p53. Compared to the classical ‘acute’ p53 binding profile, ‘chronic’ p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory ‘p53 hubs’ where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the ‘lipogenic phenotype’, a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms. 相似文献
26.
Gore VK Ma VV Tamir R Gavva NR Treanor JJ Norman MH 《Bioorganic & medicinal chemistry letters》2007,17(21):5825-5830
A novel series of 4,5-biarylimidazoles as TRPV1 antagonists were designed based on the previously reported 4,6-disubstituted benzimidazole series. The analogs were evaluated for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. These studies led to the identification of a highly potent and orally bioavailable TRPV1 antagonist, imidazole 33. 相似文献
27.
Secretins form megadalton bacterial-membrane channels in at least four sophisticated multiprotein systems that are crucial for translocation of proteins and assembled fibers across the outer membrane of many species of bacteria. Secretin subunits contain multiple domains, which interact with numerous other proteins, including pilotins, secretion-system partner proteins, and exoproteins. Our understanding of the structure of secretins is rapidly progressing, and it is now recognized that features common to all secretins include a cylindrical arrangement of 12-15 subunits, a large periplasmic vestibule with a wide opening at one end and a periplasmic gate at the other. Secretins might also play a key role in the biogenesis of their cognate secretion systems. 相似文献
28.
Reichow SL Korotkov KV Gonen M Sun J Delarosa JR Hol WG Gonen T 《Channels (Austin, Tex.)》2011,5(3):215-218
The type II secretion system (T2SS) is a large macromolecular complex spanning the inner and outer membranes of many Gram-negative bacteria. The T2SS is responsible for the secretion of virulence factors such as cholera toxin (CT) and heat-labile enterotoxin (LT) from Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. CT and LT are closely related AB5 heterohexamers, composed of one A subunit and a B-pentamer. Both CT and LT are translocated, as folded protein complexes, from the periplasm across the outer membrane through the type II secretion channel, the secretin GspD. We recently published the 19 Å structure of the V. cholerae secretin (VcGspD) in its closed state and showed by SPR measurements that the periplasmic domain of GspD interacts with the B-pentamer complex. Here we extend these studies by characterizing the binding of the cholera toxin B-pentamer to VcGspD using electron microscopy of negatively stained preparations. Our studies indicate that the pentamer is captured within the large periplasmic vestibule of VcGspD. These new results agree well with our previously published studies and are in accord with a piston-driven type II secretion mechanism.Key words: secretin, GspD, electron cryomicroscopy, type II secretion system (T2SS), cholera toxin 相似文献
29.
30.
Associations between δ13C values and leaf gas exchanges and tree-ring or needle growth, used in ecophysiological compositions, can be complex depending
on the relative timing of CO2 uptake and subsequent redistribution and allocation of carbon to needle and stem components. For palaeoenvironmental and
dendroecological studies it is often interpreted in terms of a simple model of δ13C fractionation in C3 plants. However, in spite of potential complicating factors, few studies have actually examined these relationships in mature
trees over inter- and intra-annual time-scales. Here, we present results from a 4 years study that investigated the links
between variations in leaf gas-exchange properties, growth, and dated δ13C values along the needles and across tree rings of Aleppo pine trees growing in a semi-arid region under natural conditions
or with supplemental summer irrigation. Sub-sections of tissue across annual rings and along needles, for which time of formation
was resolved from growth rate analyses, showed rapid growth and δ13C responses to changing environmental conditions. Seasonal cycles of growth and δ13C (up to ~4‰) significantly correlated (P<0.01) with photosynthetically active radiation, vapour pressure deficit, air temperature, and soil water content. The irrigation
significantly increased leaf net assimilation, stomatal conductance and needle and tree-ring growth rate, and markedly decreased
needle and tree-ring δ13C values and its sensitivity to environmental parameters. The δ13C estimates derived from gas-exchange parameters, and weighted by assimilation, compared closely with seasonal and inter-annual
δ13C values of needle- and tree-ring tissue. Higher stomatal conductances of the irrigated trees (0.22 vs. 0.08 mol m−2 s−1 on average) corresponded with ~2.0‰ lower average δ13C values, both measured and derived. Derived and measured δ13C values also indicated that needle growth, which occurs throughout the stressful summer was supported by carbon from concurrent,
low rate assimilation. For Aleppo pine under semi-arid and irrigated conditions, the δ13C of tree-ring and needle material proved, in general, to be a reasonable indicator of integrated leaf gas-exchange properties. 相似文献