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1.
Activation of human neutrophil gelatinase by endogenous serine proteinases. 总被引:3,自引:0,他引:3 下载免费PDF全文
The role of serine proteinases and oxidants in the activation of gelatinase released from human neutrophils was investigated. Gelatinase was measured by its ability to degrade both gelatin and native glomerular basement-membrane type IV collagen. When fMet-Leu-Phe or phorbol 12-myristate 13-acetate was used to stimulate the neutrophils, no gelatinase activity was measured in the absence of a mercurial activator, indicating that the enzyme was released entirely in latent form. However, when fMet-Leu-Phe-stimulated cells were treated with cytochalasin B, 50-70% of the maximal gelatinase activity was released. Activation was blocked by the serine-proteinase inhibitor phenylmethanesulphonyl fluoride and a specific inhibitor of neutrophil elastase, but was not affected by an inhibitor of cathepsin G. Addition of catalase or azide to prevent oxidative reactions did not affect activation of gelatinase under any conditions of stimulation, indicating that oxidants were not involved in activation. Our results imply that oxidative activation of gelatinase does not occur readily. However, neutrophil serine proteinases, particularly elastase, provide an alternative and apparently more efficient mechanism of activation. 相似文献
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A heterologous lectin-enzyme immunoassay is described. Microtiter plate wells were coated with affinity-purified antibodies to human transferrin. After incubation with transferrin sialovariants, prepared by limited neuraminidase treatment and separated with chromatofocusing, a lectin-enzyme-streptavidin complex was added. A good correlation was obtained between the number of terminal galactose groups on transferrin and the response in the lectin-enzyme immunoassay using Ricinus communis agglutinin as the galactose-binding lectin. The results indicate that characterization of glycosylation is possible with less than a microgram of the glycoprotein available, using lectin-enzyme immunoassays. 相似文献
4.
A. Urrestarazu S. Vissers I. Iraqui M. Grenson 《Molecular & general genetics : MGG》1998,257(2):230-237
This paper reports the first isolation of Saccharomyces cerevisiae mutants lacking aromatic aminotransferase I activity (aro8), and of aro8 aro9 double mutants which are auxotrophic for both phenylalanine and tyrosine, because the second mutation, aro9, affects aromatic aminotransferase II. Neither of the single mutants displays any nutritional requirement on minimal ammonia
medium. In vitro, aromatic aminotransferase I is active not only with the aromatic amino acids, but also with methionine,
α-aminoadipate, and leucine when phenylpyruvate is the amino acceptor, and in the reverse reactions with their oxo-acid analogues
and phenylalanine as the amino donor. Its contribution amounts to half of the glutamate:2-oxoadipate activity detected in
cell-free extracts and the enzyme might be identical to one of the two known α-aminoadipate aminotransferases. Aromatic aminotransferase
I has properties of a general aminotransferase which, like several aminotransferases of Escherichia coli, may be able to play a role in several otherwise unrelated metabolic pathways. Aromatic aminotransferase II also has a broader
substrate specificity than initially described. In particular, it is responsible for all the measured kynurenine aminotransferase
activity. Mutants lacking this activity grow very slowly on kynurenine medium.
Received: 21 October 1996 / Accepted: 23 September 1997 相似文献
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Novel approaches for the qualitative and quantitative proteomics analysis by nanoscale LC-MS applied to the study of protein expression response in depleted and undepleted serum of Gaucher patients undergoing enzyme replacement therapy are presented. Particular emphasis is given to the method reproducibility of these LC-MS experiments without the use of isotopic labels. The level of chitotriosidase, an established Gaucher biomarker, was assessed by means of an absolute concentration determination technique for alternate scanning LC-MS generated data. Disease associated proteins, including fibrinogens, complement cascade proteins, and members of the high density lipoprotein serum content, were recognized by various clustering methods and sorting and intensity profile grouping of identified peptides. Condition-unique LC-MS protein signatures could be generated utilizing the measured serum protein concentrations and are presented for all investigated conditions. The clustering results of the study were also used as input for gene ontology searches to determine the correlation between the molecular functions of the identified peptides and proteins. 相似文献
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Rodenburg J Vissers MN Wiegman A Trip MD Bakker HD Kastelein JJ 《Current opinion in lipidology》2004,15(4):405-411
PURPOSE OF THIS REVIEW: This review provides an update on recent advances in the diagnosis and management of children with familial hypercholesterolemia. RECENT FINDINGS: A large cross-sectional cohort study of paediatric familial hypercholesterolemia demonstrated that affected children had a 5-fold more rapid increase of carotid arterial wall intima-media thickness during childhood years than their affected siblings. This faster progression led to a significant deviation in terms of intima-media thickness from the age of 12 years and onwards. Low-density lipoprotein cholesterol was a strong and independent predictor of carotid artery intima-media thickness in these children, which confirms the pivotal role of low-density lipoprotein cholesterol for the development of atherosclerosis. In this condition lipid lowering by statin therapy is accompanied by carotid intima-media thickness regression in familial-hypercholesterolemic children, which suggests that initiation of low-density lipoprotein cholesterol-reducing medication in childhood already can inhibit or possibly reduce the faster progression of atherosclerosis. Furthermore, these trials demonstrated that statins are safe and do not impair growth or sexual development in these children. Conversely, products containing plant sterols reduced low-density lipoprotein cholesterol levels by 14%, but did not improve endothelial dysfunction as assessed by flow-mediated dilatation. SUMMARY: Children with familial hypercholesterolemia clearly benefit from lipid-lowering strategies. Statins are safe agents and have been proven to reduce elevated low-density lipoprotein cholesterol levels significantly. In addition, statins improve surrogate markers for atherosclerosis. Therefore these agents should become the pivotal therapy in children with familial hypercholesterolemia. 相似文献
9.
Vissers LE Stankiewicz P Yatsenko SA Crawford E Creswick H Proud VK de Vries BB Pfundt R Marcelis CL Zackowski J Bi W van Kessel AG Lupski JR Veltman JA 《Human genetics》2007,121(6):697-709
Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more
complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of
the chromosomal breakpoints and mechanisms involved. Here, we report a molecular cytogenetic analysis of two patients with
congenital anomalies and unbalanced de novo CCRs involving chromosome 17p using high-resolution array-based comparative genomic
hybridization (array CGH) and fluorescent in situ hybridization (FISH). In the first patient, a 4-month-old boy with developmental
delay, hypotonia, growth retardation, coronal synostosis, mild hypertelorism, and bilateral club feet, we found a duplication
of the Charcot-Marie–Tooth disease type 1A and Smith-Magenis syndrome (SMS) chromosome regions, inverted insertion of the
Miller-Dieker lissencephaly syndrome region into the SMS region, and two microdeletions including a terminal deletion of 17p.
The latter, together with a duplication of 21q22.3-qter detected by array CGH, are likely the unbalanced product of a translocation
t(17;21)(p13.3;q22.3). In the second patient, an 8-year-old girl with mental retardation, short stature, microcephaly and
mild dysmorphic features, we identified four submicroscopic interspersed 17p duplications. All 17 breakpoints were examined
in detail by FISH analysis. We found that four of the breakpoints mapped within known low-copy repeats (LCRs), including LCR17pA,
middle SMS-REP/LCR17pB block, and LCR17pC. Our findings suggest that the LCR burden in proximal 17p may have stimulated the
formation of these CCRs and, thus, that genome architectural features such as LCRs may have been instrumental in the generation
of these CCRs. 相似文献
10.
Cuddihy SL Parker A Harwood DT Vissers MC Winterbourn CC 《Free radical biology & medicine》2008,44(8):1637-1644
We have compared the abilities of ascorbate and reduced glutathione (GSH) to act as intracellular free radical scavengers and protect cells against radical-mediated lipid peroxidation. Phenoxyl radicals were generated in HL60 cells, through the action of their myeloperoxidase, by adding H2O2 and phenol. Normally cultured cells, which contain no ascorbate; cells that had been preloaded with ascorbate; and those that had been depleted of GSH with buthionine sulfoximine were investigated. Generation of phenoxyl radicals resulted in the oxidation of ascorbate and GSH. Ascorbate loss was much greater in the absence of GSH, and adding glucose gave GSH-dependent protection against ascorbate loss. Ascorbate, or glucose metabolism, had little effect on the GSH loss. Glutathionyl radical formation was detected by spin trapping with DMPO in cells lacking ascorbate, and the signal was suppressed by ascorbate loading. Addition of phenol plus H2O2 to the cells caused lipid peroxidation, as measured with C11-BODIPY. Peroxidation was greatest in cells that lacked both ascorbate and GSH. Either scavenger alone gave substantial inhibition but optimal protection was seen with both present. These results indicate that GSH and ascorbate can each act as an intracellular radical scavenger and protect against lipid peroxidation. With both present, ascorbate is preferred and acts as the ultimate radical sink for phenoxyl or glutathionyl radicals. However, GSH is still consumed by metabolically recycling dehydroascorbate. Thus, recycling scavenging by ascorbate does not spare GSH, but it does enable the two antioxidants to provide more protection against lipid peroxidation than either alone. 相似文献