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31.
Localization of Drug-Metabolizing Enzyme Activities to Blood-Brain Interfaces and Circumventricular Organs 总被引:3,自引:2,他引:1
J. F. Ghersi-Egea B. Leninger-Muller G. Suleman G. Siest A. Minn 《Journal of neurochemistry》1994,62(3):1089-1096
Abstract: The brain, with the exception of the choroid plexuses and Circumventricular organs, is partially protected from the invasion of blood-borne chemicals by the specific morphological properties of the cerebral micro-vessels, namely, the tight junctions of the blood-brain barrier. Recently, several enzymes that are primarily involved in hepatic drug metabolism have been shown to exist in the brain, albeit at relatively low specific activities. In the present study, the hypothesis that these enzymes are located primarily at blood-brain interfaces, where they form an "enzymatic barrier," is tested. By using microdissection techniques or a gradient-centrifugation isolation procedure, the activities of seven drug-metabolizing enzymes in isolated microvessels, choroid plexuses, meningeal membranes, and tissue from three Circumventricular organs (the neural lobe of the hypophysis, pineal gland, and median eminence) were assayed. With two exceptions, the activities of these enzymes were higher in the three Circumventricular organs and cerebral microvessel than in the cortex. Very high membrane-bound epoxide hydrolase and UDP-glucuronosyltransferase activities (approaching those in liver) and somewhat high 7-benzoxyre-sorufin- O -dealkylase and NADPH-cytochrome P-450 reductase activities were determined in the choroid plexuses. The pia-arachnoid membranes, but not the dura matter, displayed drug-metabolizing enzyme activities, notably that of epoxide hydrolase: The drug-metabolizing enzymes located at these nonparenchymal sites may function to protect brain tissue from harmful compounds. 相似文献
32.
艾氏剂环氧化酶及细胞色素P-450对小菜蛾抗药性发展的影响 总被引:1,自引:0,他引:1
本文对室内长期饲养的小菜蛾(Plutella xylostella L.)敏感品系和田间采集的抗性种群体内的艾氏剂平氧化酶及细胞色素P-450进行了比较研究。结果证明,艾氏剂环氧化酶在感性和抗性小菜蛾间存在着量及质的差异。抗性种群的艾氏剂环氧化酶的Vmax和Km值分别为感性品系的5.4%和6.5倍。抗性种群的细胞色素P-450的含量是感性品系的1.1—1.3倍。艾氏剂环氧化酶在量上及质上的差异及细胞色素P-450含量的提高是导致小菜蛾抗药性发生与发展的重要机制之一。而且质的差异较之量的差异可能起着更为重要的作用. 相似文献
33.
J. De Kok C. Van Der Schoot M. Veldhuizen H. Th. Wolterbeek 《Biological trace element research》1993,38(1):13-26
The in vitro uptake of zinc by erythrocytes was measured under near-physiological conditions, using65Zn as a radioactive tracer. Because of the presence of serum albumin—a strong zinc ligand—a low concentration of medium free
zinc was maintained. Under these conditions a high-affinity carrier for zinc transport over the cell membrane was identified.
With human erythrocytes, a Michaelis constant (K
m
) of 0.2 nM with respect to free medium zinc was measured and aV
max
of 4.5 nmoles Zn transported per h/g dry wt. TheK
m
for medium Zn increases when the size of the internal erythrocytic Zn pool is augmented, whereasV
max
remains virtually unchanged. A model to explain this phenomenon is proposed. It is suggested that this phenomenon could underlie
observations, confirmed here, that the in vitro uptake of Zn by animal erythrocytes depends on the Zn status of the animal. 相似文献
34.
生物素标记HBV RNA探针的制备及应用 总被引:1,自引:0,他引:1
本文首次采用SP65特殊质粒与人类的乙型肝炎病毒DNA重组,制备了Bio-HBV RNA探针,能特异地与HBV DNA杂交,将该探针与缺口转移方法标记的Bio-HBV DNA探针进行了比较,结果显示出Bio-HBV RNA探针比Bio-HBV DNA探针的敏感性提高10倍,并分别应用两种探针同时检测70例乙肝病人血清中HBV DNA,阳性率各为31.42%、28.57%(P>0.25)。对Bio- 相似文献
35.
Neuronotypic Differentiation Results in Reduced Levels and Altered Distribution of Synaptophysin in PC 12 Cells 总被引:1,自引:0,他引:1
Abstract: Several synaptic vesicle proteins including synap-tophysin and p65/synaptotagmin are expressed by the pheochromocytoma cell line PC12. Stimulation of these cells with nerve growth factor for 7 days induces morphologic neuronotypic differentiation, but the levels of synaptophysin are markedly reduced. Stimulation with cyclic AMP analogs also produces neuronotypic differentiation of PC12 cells, and the degree of morphologic differentiation induced by these agents parallels their ability to effect reduction in synaptophysin levels. By contrast, levels of p65/synaptotagmin are increased following neuronotypic differentiation. The contrasting effects of neuronotypic differentiation on levels of synaptophysin and p65/synaptotagmin indicate potential differences in the regulation of these proteins in PC12 cells. Immunocytochemical labeling of undifferentiated PC12 cells reveals concentrations of synaptophysin in the perinuclear region. After neuronotypic differentiation, there is reduction in perinuclear labeling and concentration of label in swellings along PC12 cell processes. At the ultra-structural level, synaptophysin labeling is found on similar organelles in both undifferentiated and nerve growth factor-stimulated PC12 cells. Although the highest labeling densities were seen on small clear vesicles, specific labeling was also seen on dense core vesicles. The presence of synaptophysin on both small clear vesicles and dense core vesicles indicates potential functional similarities in these vesicle types. The changes in the levels and immunocytochemical distribution of synaptophysin after neuronotypic differentiation suggest possible functional heterogeneity among morphologically similar populations of small clear vesicles. 相似文献
36.
This article presents for the first time a modified protocol for RNase protection analysis that allows the substitution of32P with33P without loss of the high sensitivity of this method achieved with32P. With this protocol, we were able to detect at least 1 pg of specific mRNA. In the RNase protection analysis33P labeled riboprobes are more advantageous with regard to an easier handling and better resolution. 相似文献
37.
Peter Ort Igor A. Zalunin Victor S. Gasparov Galina G. Chestukhina Valentin M. Stepanov 《Journal of Protein Chemistry》1995,14(4):241-249
Denaturation ofBacillus thuringiensis CryIIIA-endotoxin—an insecticidal protein, active againstColeoptera larvae—in concentrated guanidine hydrochloride solutions was pursued by fluorescence and circular dichroism spectroscopy and limited proteolysis. It was found that the protein consists of two fragments that differ by their stability to denaturation by guanidine hydrochloride atpH 3. The less stable fragment corresponds to the N-terminal-helical domain limited by Leu-279; the more stable one starts with Ile-280, contains about 330 amino acid residues, and corresponds to the molecule C-terminal moiety that consist of its two-structural domains forming a superdomain.Abbreviations BT
Bacillus thuringiensis
- Gdn-HCl
guanidine hydrochloride
- PAGE
electrophoresis in polyacrylamide gel
- SDS
sodium dodecylsulfate
- CD
circular dichroism 相似文献
38.
Michael Böhm 《Molecular and cellular biochemistry》1995,147(1-2):147-160
Alterations of receptor-G-protein-regulated adenylyl cyclase activity have been suggested to represent an important alteration leading to contractile dysfunction in the failing human heart. Recent experiments suggest that the 1-adrenoceptor(1AR) density and mRNA levels are reduced, while 2-adrenoceptors and stimulatory G-proteins are unchanged (mRNA and protein level). Functional assays demonstrated that the catalyst of the adenylyl cyclase is not different between failing and nonfailing myocardium. Inhibitory G-proteins are increased (pertussis toxin substrates, protein and mRNA) and correlate to the reduced inotropic effects of -adrenoceptor agonists and of CAMP-PDE inhibitors. Gi-coupled m-cholinoceptors and A1-adrenergic receptors are unchanged in density and affinity. Stimulation of these receptors resulted in an unchanged antiadrenergic effect on force of contraction. In conclusion, a downregulation of 1-AR and an increase of Gi have been observed as signal transduction alteration in failing human myocardium. These alterations are due to alterations of gene expression in the failing heart and are related to a defective regulation of force of contraction in heart failure. 相似文献
39.
Electron transport has been studied by flash absorption and EPR spectroscopies at 10–30 K in Photosystem I particles prepared with digitonin under different redox conditions. In the presence of ascorbate, an irreversible charge separation is progressively induced at 10 K between P-700 and iron-sulfur center A by successive laser flashes, up to a maximum which corresponds to about two-thirds of the reaction centers. In these centers, heterogeneity of the rate for center A reduction is also shown. In the other third of reaction centers, the charge separation is reversible and relaxes with a t1/2 ≈ 120 μs. When the iron-sulfur centers A and B are prereduced, the 120 μs relaxation becomes the dominant process (70–80% of the reaction centers), while a slow component (t1/2 = 50–400 ms) reflecting the recombination between P-700+ and center X− occurs in a minority of reaction centers (10–15%). Flash absorption and EPR experiments show that the partner of P-700+ in the 120 μs recombination is neither X nor a chlorophyll but more probably the acceptor A−1 as defined by Bonnerjea and Evans (Bonnerjea, J. and Evans, M.C.W. (1982) FEBS Lett. 148, 313–316). The role of center X in low-temperature electron flow is also discussed. 相似文献
40.
The ratio of Photosystem (PS) II to PS I electron-transport capacity in spinach chloroplasts was compared from reaction-center and steady-state rate measurements. The reaction-center electron-transport capacity was based upon both the relative concentrations of the PS IIα, PS IIβ and PS I centers, and the number of chlorophyll molecules associated with each type of center. The reaction-center ratio of total PS II to PS I electron-transport capacity was about 1.8:1. Steady-state electron-transport capacity data were obtained from the rate of light-induced absorbance-change measurements in the presence of ferredoxin-NADP+, potassium ferricyanide and 2,5-dimethylbenzoquinone (DMQ). A new method was developed for determining the partition of reduced DMQ between the thylakoid membrane and the surrounding aqueous phase. The ratio of membrane-bound to aqueous DMQH2 was experimentally determined to be 1.3:1. When used at low concentrations (200 μM), potassium ferricyanide is shown to be strictly a PS I electron acceptor. At concentrations higher than 200 μM, ferricyanide intercepted electrons from the reducing side of PS II as well. The experimental rates of electron flow through PS II and PS I defined a PS II/PS I electron-transport capacity ratio of 1.6:1. 相似文献