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131.
Agnihotri VK Thappa RK Meena B Kapahi BK Saxena RK Qazi GN Agarwal SG 《Phytochemistry》2004,65(16):2411-2413
Fresh aerial parts of Angelica glauca, growing wild in Kashmir valley in higher Himalaya (Jammu and Kashmir, India), collected at flowering stage from different locations, on hydro-distillation provided a refreshing light pale coloured essential oil with characteristic floral woody flavour. The oil was found to be a complex mixture of mono- and sesquiterpenes and 34 compounds accounting for nearly 97.4% of the oil were characterized with the help of capillary GC, GC-MS, and NMR. Major compounds of the oil were characterized as alpha-phellandrene (13.5%), trans-carveol (12.0%), beta-pinene (11.7%), thujene (7.5%), beta-caryophyllene oxide (7.2%), beta-caryophyllene (7.0%), gamma-terpinene (6.7%), nerolidol (6.5%), beta-bisabolene (5.2%) and germacrene D (4.5%). It is the first report to exploit the essential oil from Himalayan A. glauca herb collected at flowering stage. 相似文献
132.
133.
Origins of chromosomal rearrangement hotspots in the human genome: evidence from the <Emphasis Type="Italic">AZFa</Emphasis>deletion hotspots 总被引:1,自引:1,他引:0
Background
The origins of the recombination hotspots that are a common feature of both allelic and non-allelic homologous recombination in the human genome are poorly understood. We have investigated, by comparative sequencing, the evolution of two hotspots of non-allelic homologous recombination on the Y chromosome that lie within paralogous sequences known to sponsor deletions resulting in male infertility. 相似文献134.
P-type ATPase heavy metal transporters with roles in essential zinc homeostasis in Arabidopsis 总被引:20,自引:0,他引:20
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Hussain D Haydon MJ Wang Y Wong E Sherson SM Young J Camakaris J Harper JF Cobbett CS 《The Plant cell》2004,16(5):1327-1339
Arabidopsis thaliana has eight genes encoding members of the type 1B heavy metal–transporting subfamily of the P-type ATPases. Three of these transporters, HMA2, HMA3, and HMA4, are closely related to each other and are most similar in sequence to the divalent heavy metal cation transporters of prokaryotes. To determine the function of these transporters in metal homeostasis, we have identified and characterized mutants affected in each. Whereas the individual mutants exhibited no apparent phenotype, hma2 hma4 double mutants had a nutritional deficiency phenotype that could be compensated for by increasing the level of Zn, but not Cu or Co, in the growth medium. Levels of Zn, but not other essential elements, in the shoot tissues of a hma2 hma4 double mutant and, to a lesser extent, of a hma4 single mutant were decreased compared with the wild type. Together, these observations indicate a primary role for HMA2 and HMA4 in essential Zn homeostasis. HMA2promoter- and HMA4promoter-reporter gene constructs provide evidence that HMA2 and HMA4 expression is predominantly in the vascular tissues of roots, stems, and leaves. In addition, expression of the genes in developing anthers was confirmed by RT-PCR and was consistent with a male-sterile phenotype in the double mutant. HMA2 appears to be localized to the plasma membrane, as indicated by protein gel blot analysis of membrane fractions using isoform-specific antibodies and by the visualization of an HMA2-green fluorescent protein fusion by confocal microscopy. These observations are consistent with a role for HMA2 and HMA4 in Zn translocation. hma2 and hma4 mutations both conferred increased sensitivity to Cd in a phytochelatin-deficient mutant background, suggesting that they may also influence Cd detoxification. 相似文献
135.
Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly 总被引:15,自引:0,他引:15
Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are necessary for lipoprotein assembly. ApoB consists of five structural domains, betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3). We propose that MTP contains three structural motifs (N-terminal beta-barrel, central alpha-helix, and C-terminal lipid cavity) and three functional domains (lipid transfer, membrane associating, and apoB binding). MTP's lipid transfer activity is required for the assembly of lipoproteins. This activity renders nascent apoB secretion-competent and may be involved in the import of triglycerides into the lumen of endoplasmic reticulum. In addition, MTP binds to apoB with high affinity involving ionic interactions. MTP interacts at multiple sites in the N-terminal betaalpha(1) structural domain of apoB. A novel antagonist that inhibits apoB-MTP binding decreases apoB secretion. Furthermore, site-directed mutagenesis and deletion analyses that inhibit apoB-MTP binding decrease apoB secretion. Lipids modulate protein-protein interactions between apoB and MTP. Lipids associated with MTP increase apoB-MTP binding whereas lipids associated with apoB decrease this binding. Thus, specific antagonist, site-directed mutagenesis, deletion analyses, and modulation studies support the notion that apoB-MTP binding plays a role in lipoprotein biogenesis. However, specific steps in lipoprotein assembly that require apoB-MTP binding have not been identified. ApoB-MTP binding may be important for the prevention of degradation and lipidation of nascent apoB. 相似文献
136.
Deng C Radu C Diab A Tsen MF Hussain R Cowdery JS Racke MK Thomas JA 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):2833-2842
Infections often precede the development of autoimmunity. Correlation between infection with a specific pathogen and a particular autoimmune disease ranges from moderately strong to quite weak. This lack of correspondence suggests that autoimmunity may result from microbial activation of a generic, as opposed to pathogen-specific host-defense response. The Toll-like receptors, essential to host recognition of microbial invasion, signal through a common, highly conserved pathway, activate innate immunity, and control adaptive immune responses. To determine the influence of Toll/IL-1 signaling on the development of autoimmunity, the responses of wild-type (WT) mice and IL-1R-associated kinase 1 (IRAK1)-deficient mice to induction of experimental autoimmune encephalomyelitis were compared. C57BL/6 and B6.IRAK1-deficient mice were immunized with MOG 35-55/CFA or MOG 35-55/CpG DNA/IFA. WT animals developed severe disease, whereas IRAK1-deficient mice were resistant to experimental autoimmune encephalomyelitis, exhibiting little or no CNS inflammation. IRAK1-deficient T cells also displayed impaired Th1 development, particularly during disease induction, despite normal TCR signaling. These results suggest that IRAK1 and the Toll/IL-1 pathway play an essential role in T cell priming, and demonstrate one means through which innate immunity can control subsequent development of autoimmunity. These findings may also help explain the association between antecedent infection and the development or exacerbations of some autoimmune diseases. 相似文献
137.
138.
Multiple,independently regulated pathways of cholesterol transport across the intestinal epithelial cells 总被引:3,自引:0,他引:3
The present study provides a new understanding about the mechanisms involved in cholesterol absorption by the intestinal cells. Contrary to general belief, our data show that newly absorbed cholesterol is neither immediately available for secretion with apoB lipoproteins nor exclusively secreted as part of chylomicrons. Based on our data, cholesterol transport by enterocytes can be broadly classified into two independently modulated, apoB-dependent and -independent, pathways. Cholesterol secretion by the apoB-dependent pathway is induced by oleic acid, is repressed by microsomal triglyceride transfer protein inhibitors, and occurs only with larger apoB-containing lipoproteins. ApoB-independent pathways do not require microsomal triglyceride transfer protein and involve efflux mediated by ABCA1, high density lipoprotein assembly, and possibly other unknown mechanisms. There are at least two different metabolic pools of cholesterol. The newly absorbed and pre-absorbed cholesterol are preferentially secreted via apoB-independent and apoB-dependent pathways, respectively. In contrast to compartmentalization for secretion, these two metabolic pools are equally accessible for cellular esterification. The esterified cholesterol is mainly secreted by the apoB-dependent pathway, whereas both the pathways are involved in the secretion of free cholesterol. Thus, enterocytes transport exogenous cholesterol by several independently regulated pathways raising the possibility that targeting of apoB-independent pathways may result in selective inhibition of cholesterol transport without affecting triglyceride transport. 相似文献
139.
Hussain I Hawkins J Shikotra A Riddell DR Faller A Dingwall C 《The Journal of biological chemistry》2003,278(38):36264-36268
Generation of the amyloid peptide through proteolytic processing of the amyloid precursor protein by beta- and gamma-secretases is central to the etiology of Alzheimer's disease. beta-secretase, known more widely as the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), has been identified as a transmembrane aspartic proteinase, and its ectodomain has been reported to be cleaved and secreted from cells in a soluble form. The extracellular domains of many diverse proteins are known to be cleaved and secreted from cells by a process known as ectodomain shedding. Here we confirm that the ectodomain of BACE1 is secreted from cells and that this processing is up-regulated by agents that activate protein kinase C. A metalloproteinase is involved in the cleavage of BACE1 as hydroxamic acid-based metalloproteinase inhibitors abolish the release of shed BACE1. Using potent and selective inhibitors, we demonstrate that ADAM10 is a strong candidate for the BACE1 sheddase. In addition, we show that the BACE1 sheddase is distinct from alpha-secretase and, importantly, that inhibition of BACE1 shedding does not influence amyloid precursor protein processing at the beta-site. 相似文献
140.
Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells 总被引:15,自引:0,他引:15
Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent present in green tea, is a promising chemopreventive agent. We recently showed that green tea polyphenols exert remarkable preventive effects against prostate cancer in a mouse model and many of these effects are mediated by the ability of polyphenols to induce apoptosis in cancer cells [Proc. Natl. Acad. Sci. USA 98 (2001) 10350]. Earlier, we showed that EGCG causes a G0/G1 phase cell cycle arrest and apoptosis of both androgen-sensitive LNCaP and androgen-insensitive DU145 human prostate carcinoma cells, irrespective of p53 status [Toxicol. Appl. Pharmacol. 164 (2000) 82]. Here, we provide molecular understanding of this effect. We tested a hypothesis that EGCG-mediated cell cycle dysregulation and apoptosis is mediated via modulation of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery. As shown by immunoblot analysis, EGCG treatment of LNCaP and DU145 cells resulted in significant dose- and time-dependent (i) upregulation of the protein expression of WAF1/p21, KIP1/p27, INK4a/p16, and INK4c/p18, (ii) down-modulation of the protein expression of cyclin D1, cyclin E, cdk2, cdk4, and cdk6, but not of cyclin D2, (iii) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27, and (iv) decrease in the binding of cyclin E toward cdk2. Taken together, our results suggest that EGCG causes an induction of G1 phase ckis, which inhibits the cyclin-cdk complexes operative in the G0/G1 phase of the cell cycle, thereby causing an arrest, which may be an irreversible process ultimately leading to apoptotic cell death. This is the first systematic study showing the involvement of each component of cdk inhibitor-cyclin-cdk machinery during cell cycle arrest and apoptosis of human prostate carcinoma cells by EGCG. 相似文献