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排序方式: 共有423条查询结果,搜索用时 46 毫秒
101.
Shengli Shi Francesca N Hudson Dianne Botta Monica B McGrath Collin C White Haley D Neff-LaFord Michael J Dabrowski Narendra P Singh Terrance J Kavanagh 《Cytometry. Part A》2007,71(9):686-692
Hydrogen peroxide (H2O2) can cause single strand DNA breaks (ssDNA) in cells when the mechanisms normally in place to reduce it are overwhelmed. Such mechanisms include catalase, glutathione peroxidases (GPx), and peroxiredoxins. The relative importance of these enzymes in H2O2 reduction varies with cell and tissue type. The role of the GPx cofactor glutathione (GSH) in oxidative defense can be further understood by modulating its synthesis. The first and rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), which has a catalytic subunit (Gclc) and a modifier subunit (Gclm). Using mouse hepatoma cells we evaluated the effects of GCL over expression on H2O2-induced changes in GSH and ssDNA break formation with the single cell gel electrophoresis assay (SCG or comet assay), and the acridine orange DNA unwinding flow cytometry assay (AO unwinding assay). Cells over expressing GCL had higher GSH content than control cells, and both SCG and AO unwinding assays revealed that cells over expressing GCL were significantly more resistant to H2O2-induced ssDNA break formation. Furthermore, using the AO unwinding assay, the prevalence of H2O2-induced breaks in different phases of the cell cycle was not different, and the degree of protection afforded by GCL over expression was also not cell cycle phase dependent. Our results support the hypothesis that GCL over expression enhanced GSH biosynthesis and protected cells from H2O2-induced DNA breaks. These results also suggest that genetic polymorphisms that affect GCL expression may be important determinants of oxidative DNA damage and cancer. 相似文献
102.
Krzywanski DM Dickinson DA Iles KE Wigley AF Franklin CC Liu RM Kavanagh TJ Forman HJ 《Archives of biochemistry and biophysics》2004,423(1):116-125
Glutamate cysteine ligase (GCL), composed of a catalytic (GCLC) and modulatory (GCLM) subunit, catalyzes the first step of glutathione (GSH) biosynthesis. Using 4-hydroxy-2-nonenal (4HNE), 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), and tertiary-butylhydroquinone (tBHQ) as models of oxidative stress which are known to work through different mechanisms, we measured changes in cellular GSH, GCL mRNA, and GCL protein. 4HNE and tBHQ treatments increased cellular GSH levels, while DMNQ exposure depleted GSH. Furthermore, changes in the two GCL mRNAs largely paralleled changes in the GCL proteins; however, the magnitudes differed, suggesting some form of translational control. The molar ratio of GCLC:GCLM ranged from 3:1 to 17:1 in control human bronchial epithelial (HBE1) cells and all treatments further increased this ratio. Data from several mouse tissues show molar ratios of GCLC:GCLM that range from 1:1 to 10:1 in support of these findings. These data demonstrate that alterations in cellular GSH are clearly correlated with GCLC to a greater extent than GCLM. Surprisingly, both control HBE1 cells and some mouse tissues have more GCLC than GCLM and GCLM increases to a much lesser extent than GCLC, suggesting that the regulatory role of GCLM is minimal under physiologically relevant conditions of oxidative stress. 相似文献
103.
Effective inhibition of K(b)- and D(b)-restricted antigen presentation in primary macrophages by murine cytomegalovirus 总被引:4,自引:0,他引:4
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LoPiccolo DM Gold MC Kavanagh DG Wagner M Koszinowski UH Hill AB 《Journal of virology》2003,77(1):301-308
Macrophages play an important role in murine cytomegalovirus (MCMV) infection in vivo, both in disseminating infection and in harboring latent virus. MCMV encodes three immune evasion genes (m4, m6, and m152) that interfere with the ability of cytotoxic T cells (CTL) to detect virus-infected fibroblasts, but the efficacy of immune evasion in macrophages has been controversial. Here we show that MCMV immune evasion genes function in H-2(b) primary bone marrow macrophages (BMMphi) in the same way that they do in fibroblasts. Metabolic labeling experiments showed that class I is retained in the endoplasmic reticulum by MCMV infection and associates with m4/gp34 to a similar extent in fibroblasts and BMMphi. We tested a series of K(b)- and D(b)-restricted CTL clones specific for MCMV early genes against a panel of MCMV wild-type virus and mutants lacking m152, m4, or m6. MCMV immune evasion genes effectively inhibited antigen presentation. m152 appeared sufficient to abolish D(b)-restricted presentation in infected macrophages, as has been previously observed in infected fibroblasts. However, for inhibition of recognition of infected macrophages by K(b)-restricted CTL, m4, m6, and m152 were all required. The contribution of m4 to inhibition of recognition appeared much more important in macrophages than in fibroblasts. Thus, MCMV immune evasion genes function effectively in primary macrophages to prevent CTL recognition of early antigens and show the same pattern of major histocompatibility complex class I allele discrimination as is seen in fibroblasts. Furthermore, for inhibition of K(b)-restricted presentation, a strong synergistic effect was noted among m152, m4, and m6. 相似文献
104.
Incompatible plant-pathogen interactions result in the rapid cell death response known as hypersensitive response (HR) and activation of host defense related genes. To understand the cellular mechanism controlling defense response better, a novel pathogenesis-related (PR) gene and putative cell wall protein gene, CaTin2, was isolated through differential screening of a hot pepper cDNA library and characterized. CaTin2 gene was locally and systemically induced in hot pepper plants upon TMV-P0 inoculation which induces HR. However, CaTin2 gene wasn't regulated by bacterial HR-specific signal pathway. The full-length cDNA for CaTin2, which is 864 nucleotides long, contained the open reading frame of 200 amino acids including cell wall targeting sequences of 26 amino acids. CaTin2 gene has no sequence similarity with other cell wall protein genes except the signal sequence and exists as only one copy in hot pepper genome. CaTin2 gene contains repeated helix-turn-helix motif consisting of 39 amino acids. CaTin2 mRNA accumulation was induced in response to various treatments such as ethylene, SA, MeJA, ABA, methyl viologen, NaCl and wounding at early time points. Subcelluar localization of CaTin2 was confirmed in the cell wall in hot pepper leaves by making CaTin2::smGFP fusion protein. The transgenic plants overexpressing CaTin2 cDNA were resistant to TMV and CMV inoculation. From these results, CaTin2 gene may encode a virus-related new cell wall protein member. 相似文献
105.
Tongli?WangEmail author Sally?N.?Aitken Kathleen?L.?Kavanagh 《Trees - Structure and Function》2003,17(3):269-277
Selection for both growth and wood quality is the primary goal of many tree breeding programs. In order to investigate the impacts of such selection on adaptive traits, observations were made on phenology, drought resistance, xylem conductance and xylem vulnerability to cavitation of 2-year-old seedlings of lodgepole pine (Pinus contorta Dougl. Ex Loud var. latifolia Engelm) from four subpopulations: (1) fast height growth and high wood density (FH); (2) slow height growth and high density (SH); (3) fast height growth and low density (FL); and (4) slow height growth and low density (SL). Results showed that the impact of the selection on phenology was minor; differences in growth among subpopulations were mainly attributable to maximal growth rate and the duration of the period of rapid growth. The FL subpopulation showed a significantly stronger productivity decline in response to moderate drought compared to the two slower-growing subpopulations. The FH subpopulation showed significantly higher xylem specific conductivity than the two slower-growing subpopulations, and greater resistance to cavitation than the other three subpopulations, suggesting the possibility of selecting families that combine fast growth, high wood density and drought tolerance. 相似文献
106.
GUS continues to be the reporter of choice for many gene fusion applications, due to the unparalleled sensitivity of the encoded enzyme and the ease with which it can be quantified in cell-free extracts and visualized histochemically in cells and tissues. A compatible and functionally equivalent reporter gene would facilitate dual promoter studies and internal standardization of expression analyses in the same plant. A search for a candidate enzyme activity not found in plants, which might form the basis of a novel GUS-compatible reporter system, led us to investigate nanH, a Clostridium perfringens gene which encodes the so-called 'small' cytoplasmic sialidase. Expression of the native, AT-rich nanH gene in transgenic plants did not, however, result in detectable sialidase activity. For this reason, a codon-optimized derivative, NAN, was synthesized which possesses a GC content similar to that found in highly expressed plant genes. NAN enzyme activity was expressed at high levels in both stably and transiently transformed cells, possessed kinetic and stability properties similar to those of GUS, and showed optimal activity in GUS buffer. Moreover, NAN and GUS activity could be visualized simultaneously in polyacrylamide gels using the corresponding methylumbelliferone-based substrates, and in whole seedlings and tissue sections using the histochemical substrates 5-bromo-4-chloro-3-indolyl alpha-d-N-acetylneuraminic acid (X-NeuNAc) and 5-bromo-6-chloro-3-indolyl beta-d-glucuronide (X-GlucM), respectively. 相似文献
107.
Emma Kavanagh Anne C Osborne Doreen E Ashhurst Andrew A Pitsillides 《The journal of histochemistry and cytochemistry》2002,50(8):1039-1047
Changes in glycosaminoglycan (GAG) content and distribution are vital for joint development. However, their precise character has not been established. We have used immunohistochemistry (IHC) and "critical electrolyte" Alcian blue staining to assess such changes in developing chick and rabbit joints. IHC showed chondroitin sulfate labeling in chick epiphyseal cartilage but not in interzones. In contrast, prominent labeling for keratan sulfate (KS) was restricted to chick cartilage-interzone interfaces. In rabbit knees, KS labeling was also prominent at presumptive cavity borders, but weak in interzone and cartilage. Selective pre-digestion produced appropriate loss of label and undersulfated KS was undetectable. Quantification of Alcian blue staining by scanning and integrating microdensitometry showed prominent hyaluronan-like (HA-like) interzone staining, with chondroitin sulfate and weaker KS staining restricted to epiphyseal cartilage. Hyaluronidase decreased HA-like staining in the interzone. Surprisingly, keratanases also reduced HA-like but not sulfated GAG (sGAG-like) staining in the interzone. Chondroitinase ABC had little effect on HA-like staining but decreased sGAG staining in all regions. Rabbit joints also showed HA-like but not KS staining in the interzone and strong chondroitin sulfate-like staining in epiphyseal cartilage. Our findings show restricted KS distribution in the region close to the presumptive joint cavity of developing chick and rabbit joints. Alcian blue staining does not detect this moiety. Therefore, it appears that although histochemistry allows relatively insensitive quantitative assessment of GAGs, IHC increases these detection limits. This is particularly evident for KS, which exhibits immunolabeling patterns in joints from different species that is consistent with a conserved functional role in chondrogenesis. 相似文献
108.
Justin J Kavanagh Steven Morrison Rod S Barrett 《Journal of applied physiology》2006,101(4):1118-1126
The purpose of this study was to examine how inducing fatigue of the 1) lumbar erector spinae and 2) cervical erector spinae (CES) muscles affected the ability to maintain head stability during walking. Triaxial accelerometers were attached to the head, upper trunk, and lower trunk to measure accelerations in the vertical, anterior-posterior, and mediolateral directions during walking. Using three accelerometers enabled two adjacent upper body segments to be defined: the neck segment and trunk segment. A transfer function was applied to root mean square acceleration, peak power, and harmonic data derived from spectral analysis of accelerations to quantify segmental gain. The structure of upper body accelerations were examined using measures of signal regularity and smoothness. The main findings were that head stability was only affected in the anterior-posterior direction, as accelerations of the head were less regular following CES fatigue. Furthermore, following CES fatigue, the central nervous system altered the attenuation properties of the trunk segment in the anterior-posterior direction, presumably to enhance head stability. Following lumbar erector spinae fatigue, the trunk segment had greater gain and increased regularity and smoothness of accelerations in the mediolateral direction. Overall, the results of this study suggest that erector spinae fatigue differentially altered segmental attenuation during walking, according to the level of the upper body that was fatigued and the direction that oscillations were attenuated. A compensatory postural response was not only elicited in the sagittal plane, where greater segmental attenuation occurred, but also in the frontal plane, where greater segmental gain occurred. 相似文献
109.
Fucose is a major constituent of the protein- and lipid-linked glycans of
the various life-cycle stages of schistosomes. These fucosylated glycans
are highly antigenic and seem to play a role in the pathology of
schistosomiasis. In this article we describe the identification and
characterization of two fucosyltransferases (FucTs) in cercariae of the
avian schistosome Trichobilharzia ocellata, a GDP-Fuc:[Galbeta1--
>4]GlcNAcbeta-R alpha1-->3-FucT and a novel GDP-Fuc:Fucalpha-R
alpha1-- >2-FucT. Triton X-100 extracts of cercariae were assayed for
FucT activity using a variety of acceptor substrates. Type 1 chain
(Galbeta1- ->3GlcNAc) based compounds were poor acceptors, whereas those
based on a type 2 chain (Galbeta1-->4GlcNAc), whether
alpha2'-fucosylated, alpha3'-sialylated, or unsubstituted, and whether
present as oligosaccharide or contained in a glycopeptide or glycoprotein,
all served as acceptor substrates. In this respect the schistosomal alpha3-
FucT resembles human FucT V and VI rather than other known FucTs. N-
ethylmaleimide, an inhibitor of several human FucTs, had no effect on the
activity of the schistosomal alpha3-FucT, whereas GDP-beta-S was strongly
inhibitory. Large scale incubations were carried out with
Galbeta1-->4GlcNAc, GalNAcbeta1-->4GlcNAcbeta-O -(CH2)8COOCH3 and
Fucalpha1-->3GlcNAcbeta1-->2Man as acceptor substrates and the
products of the incubations were isolated using a sequence of
chromatographic techniques. By methylation analysis and 2D-TOCSY and
ROESY1H-NMR spectroscopy the products formed were shown to be Galbeta1--
>4[Fucalpha1-->2Fucalpha1-->3]GlcNAc,
GalNAcbeta1-->4[Fucalpha1-- >2Fucalpha1-->3]GlcNAcbe
ta-O-(CH2)8COOCH3, and Fucalpha1-->2Fucalpha1--
>3GlcNAcbeta1-->2Man, respectively. It is concluded that the alpha2-
FucT and alpha3-FucT are involved in the biosynthesis of the (oligomeric)
Lewisx sequences and the Fucalpha1-->2Fucalpha1-->3GlcNAc structural
element that have been described on schistosomal glycoconjugates.
相似文献
110.
Acceptor specificity of the human leukocyte alpha3 fucosyltransferase: role of FucT-VII in the generation of selectin ligands 总被引:2,自引:2,他引:0
Britten CJ; van den Eijnden DH; McDowell W; Kelly VA; Witham SJ; Edbrooke MR; Bird MI; de Vries T; Smithers N 《Glycobiology》1998,8(4):321-327
The alpha3 fucosyltransferase, FucT-VII, is one of the key
glycosyltransferases involved in the biosynthesis of the sialyl Lewis X
(sLex) antigen on human leukocytes. The sialyl Lewis X antigen
(NeuAcalpha(2-3)Galbeta(1-4)[Fucalpha(1-3)]GlcNAc-R) is an essential
component of the recruitment of leukocytes to sites of inflammation,
mediating the primary interaction between circulating leukocytes and
activated endothelium. In order to characterize the enzymatic properties of
the leukocyte alpha3 fucosyltransferase FucT-VII, the enzyme has been
expressed in Trichoplusia ni insect cells. The enzyme is capable of
synthesizing both sLexand sialyl-dimeric-Lexstructures in vitro , from
3'-sialyl-lacNAc and VIM-2 structures, respectively, with only low levels
of fucose transfer observed to neutral or 3'-sulfated acceptors. Studies
using fucosylated NeuAcalpha(2-3)-(Galbeta(1- 4)GlcNAc)3-Me acceptors
demonstrate that FucT-VII is able to synthesize both di-fucosylated and
tri-fucosylated structures from mono- fucosylated precursors, but
preferentially fucosylates the distal GlcNAc within a polylactosamine
chain. Furthermore, the rate of fucosylation of the internal GlcNAc
residues is reduced once fucose has been added to the distal GlcNAc. These
results indicate that FucT-VII is capable of generating complex selectin
ligands, in vitro , however the order of fucose addition to the lactosamine
chain affects the rate of selectin ligand synthesis.
相似文献