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排序方式: 共有367条查询结果,搜索用时 31 毫秒
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McKay A Leung BP McInnes IB Thomson NC Liew FY 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(5):2903-2908
Statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, are effective serum cholesterol-lowering agents in clinical practice, and they may also have anti-inflammatory properties. Asthma is characterized by chronic eosinophilic inflammation in the airways, which is thought to be regulated by the activity of T lymphocytes. We therefore examined the anti-inflammatory activity of simvastatin in a murine model of allergic asthma. In mice previously sensitized to OVA, simvastatin treatment, either orally or i.p., reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid in response to inhaled OVA challenge. Simvastatin therapy i.p. was also associated with a reduction in IL-4 and IL-5 levels in bronchoalveolar lavage fluid and, at higher doses, a histological reduction in inflammatory infiltrates in the lungs. OVA-induced IL-4, IL-5, IL-6, and IFN-gamma secretion was reduced in thoracic lymph node cultures from simvastatin-treated mice. Simvastatin treatment did not alter serum total IgE or OVA-specific IgG1 and IgG2a levels. These data demonstrate the therapeutic potential of statin-sensitive pathways in allergic airways disease. 相似文献
44.
Comparative genomics of Brassica oleracea and Arabidopsis thaliana reveal gene loss, fragmentation, and dispersal after polyploidy 总被引:1,自引:0,他引:1
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Town CD Cheung F Maiti R Crabtree J Haas BJ Wortman JR Hine EE Althoff R Arbogast TS Tallon LJ Vigouroux M Trick M Bancroft I 《The Plant cell》2006,18(6):1348-1359
45.
Cardiac myocyte apoptosis underlies the pathophysiology of cardiomyopathy, and plays a critical role in the transition from myocardial hypertrophy to heart failure. Angiotensin II (Ang II) induces cardiac myocyte apoptosis and hypertrophy which contribute to heart failure possibly through enhanced oxidative stress; however, the mechanisms underlying the activation of both pathways and their interactions remain unclear. In the present study, we have investigated whether overexpression of the antioxidant protein heme oxygenase-1 (HO-1) protects against apoptosis and hypertrophy in cultured rat cardiac myocytes treated with Ang II. Our findings demonstrate that Ang II (100 nM, 24 h) alone upregulates HO-1 expression and induces both myocyte hypertrophy and apoptosis, assessed by measuring terminal deoxynucleotidyltransferase dUTP nick-end labelling (TUNEL) staining, caspase-3 activity and mitochondrial membrane potential. Ang II elicited apoptosis was augmented in the presence of tin protoporphyrin, an inhibitor of HO activity, while HO-1 gene transfer to myocytes attenuated Ang II-mediated apoptosis but not hypertrophy. Adenoviral overexpression of HO-1 was accompanied by a significant increase in Ang II induced phosphorylation of Akt, however, Ang II-mediated p38 mitogen activated protein kinase (MAPK) phosphorylation was attenuated. Inhibition of phosphotidylinositol-3-kinase enhanced myocyte apoptosis elicited by Ang II, however, p38MAPK inhibition had no effect, suggesting that overexpression of HO-1 protects myocytes via augmented Akt activation and not through modulation of p38MAPK activation. Our findings identify the signalling pathways by which HO-1 gene transfer protects against apoptosis and suggest that overexpression of HO-1 in cardiomyopathies may delay the transition from myocyte hypertrophy to heart failure. 相似文献
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María Elisa Mariani Marcos Ariel Villarreal Foo Cheung Ezequiel Pedro Marcos Leiva Ricardo Román Madoery Gerardo Daniel Fidelio 《Biochimie》2012
At the present, no secreted phospholipase A2 (sPLA2) from soybean (Glycine max) was investigated in detail. In this work we identified five sequences of putative secreted sPLA2 from soybean after a BLAST search in G. max database. Sequence analysis showed a conserved PA2c domain bearing the Ca2+ binding loop and the active site motif. All the five mature proteins contain 12 cysteine residues, which are commonly conserved in plant sPLA2s. We propose a phylogenetic tree based on sequence alignment of reported plant sPLA2s including the novel enzymes from G. max. According to PLA2 superfamily, two of G. max sPLA2s are grouped as XIA and the rest of sequences as XIB, on the basis of differences found in their molecular weights and deviating sequences especially in the N- and C-terminal regions of the isoenzymes. Furthermore, we report the cloning, expression and purification of one of the putative isoenzyme denoted as GmsPLA2-XIA-1. We demonstrate that this mature sPLA2 of 114 residues had PLA2 activity on Triton:phospholipid mixed micelles and determine the kinetic parameters for this system. We generate a model based on the known crystal structure of sPLA2 from rice (isoform II), giving first insights into the three-dimensional structure of folded GmsPLA2-XIA-1. Besides describing the spatial arrangement of highly conserved pair HIS-49/ASP-50 and the Ca+2 loop domains, we propose the putative amino acids involved in the interfacial recognition surface. Additionally, molecular dynamics simulations indicate that calcium ion, besides its key function in the catalytic cycle, plays an important role in the overall stability of GmsPLA2-XIA-1 structure. 相似文献
48.
The copper(ii) complexes of two salicylaldehyde semicarbazones, HOC(6)H(4)CH[double bond, length as m-dash]N-NHCONR(2) [H(2)Bnz(2) (R = CH(2)Ph) and H(2)Bu(2) (R = Bu)], were evaluated for their DNA binding and cleavage properties by spectrophotometric DNA titration, ethidium bromide displacement assay and electrophoretic mobility shift assay. Results showed that the Cu(ii) complexes can bind to DNA via a partial intercalation mode with binding constants of 1.1 × 10(4) and 9.5 × 10(3) M(-1) for [Cu(HBnz(2))Cl] and [Cu(HBu(2))Cl], respectively. These complexes also cleave DNA in the presence of ascorbic acid, most likely through hydroxyl radicals that are generated via the reduction of a Cu(ii) to a Cu(i) species. The complexes show similar DNA cleavage activity, which is reflected in the similarity of their frontier molecular orbital energies calculated by density functional theory. These results are discussed in relation to the anticancer properties of the complexes. 相似文献
49.
McKimmie CS Fraser AR Hansell C Gutiérrez L Philipsen S Connell L Rot A Kurowska-Stolarska M Carreno P Pruenster M Chu CC Lombardi G Halsey C McInnes IB Liew FY Nibbs RJ Graham GJ 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(5):3353-3363
D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes. 相似文献
50.
Lakes in the McMurdo Dry Valleys of Antarctica are characterized by a permanent ice cover and little or no anthropogenic influence.
Although bacterial cultures have been obtained from these habitats, recent culture-independent studies indicate that the most
abundant microbes in these systems are not yet cultivated. By using dilution-to-extinction cultivation methods with sterilized
and nutrient-amended lake water as media, we isolated 148 chemotrophic psychrotolerant bacterial cultures from fresh surface
water of Lake Fryxell and the east lobe of Lake Bonney and the hypersaline, suboxic bottom water from the west lobes of Lake
Bonney. Screening of the 16S ribosomal ribonucleic acid (rRNA) genes of the cultures by restriction fragment length polymorphism
(RFLP) yielded 57 putatively pure psychrotolerant, slow growing cultures grouped into 18 clusters. The sequencing of 16S rRNA
genes of randomly selected representatives of each RFLP cluster revealed that the corresponding isolates belong to the Alphaproteobacteria (six RFLP patterns), Betaproteobacteria (six RFLP patterns), Bacteroidetes (four RFLP patterns), and Actinobacteria (two RFLP patterns). Phylogenetic analysis of the sequences showed that the vast majority of the isolates were not closely
related to previously described species. Thirteen of 18 RFLP patterns shared a 16S ribosomal deoxyribonucleic acid sequence
similarity of 97% or less with the closest described species, and four isolates had a sequence similarity of 93% or less with
the nearest described species. Phylogenetic analysis showed that these sequences were representatives of deeply branching
organisms in the respective phylum. A comparison of the isolates with 16S rRNA clone libraries prepared from the same environments
showed substantial overlap, indicating that dilution-to-extinction culturing in natural lake water media can help isolate
some of the most abundant organisms in these perennially ice-covered lakes. 相似文献