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191.
Copper deficiency was induced in rats by feeding diets containing either 62% starch, fructose or glucose deficient in copper for 6 weeks. All copper deficient rats, regardless of the dietary carbohydrate, exhibited decreased ceruloplasmin activity and decreased serum copper concentrations. Rats fed the fructose diet exhibited a more severe copper deficiency as compared to rats fed either starch or glucose. The increased severity of the deficiency was characterized by reduced body weight, serum copper concentration and hematocrit. In all rats fed the copper adequate diets, blood pressure was unaffected by the type of dietary carbohydrate. Significantly reduced systolic blood pressure was evident only in rats fed the fructose diet deficient in copper. When comparing the three carbohydrate diets, the physiological and biochemical lesions induced by copper deprivation could be magnified by feeding fructose. 相似文献
192.
Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain 总被引:6,自引:0,他引:6
A series of tetrazole convulsants were examined for their potencies in displacing [35S]-t-butylbicyclophosphorothionate (TBPS) from the picrotoxin site on the benzodiazepine-GABA-chloride ionophore receptor complex. All of the tetrazole derivatives tested inhibited [35S]-TBPS binding from rat forebrain membranes, and except for one (undecamethylenetetrazole), had Hill coefficients near unity. Similar to other chemically unrelated convulsants the inhibition of [35S]-TBPS binding by the various tetrazole derivatives was unaffected by the addition of the bicucculine-like GABA antagonist, R 5135. To ascertain whether the inhibition of specific [35S]-TBPS binding by the tetrazole derivatives was related to their convulsant properties, we compared their in vitro potencies in displacing [35S]-TBPS binding with their minimum convulsant potencies in mice. A very good correlation was observed (r = 0.96, p less than 0.001) between their relative affinities for the [35S]-TBPS binding site and their convulsant potencies, indicating that pentamethylenetetrazol and related tetrazoles may produce their convulsant and anxiogenic actions via the GABA-benzodiazepine-chloride ionophore receptor complex. 相似文献
193.
Two functional T hybridomas were prepared by fusing BW5147 with ovalbumin (OVA)-primed splenic T blast cells. One was OVA specific for helper function requiring concanavalin A supernatant (CAS) for activity while the other, termed autoreactive, was nonspecific for helper-augmenting activity. Both required H-2d presenter cells for interleukin 2 (IL-2) production. The autoreactive clone showed helper activity only in the presence of suboptimal numbers of antigen (Ag)-primed T cells. Both T hybridomas were Lyt 1+2+ and Thy 1+. Cells produced from such fusions should provide a useful instrument not only in dissecting the T-cell regulatory mechanism, but also in isolating and characterizing self-recognition structures. 相似文献
194.
Our laboratory has established that 2,4-dinitrophenyl-conjugated mouse IgG (DNP-MGG) can specifically suppress the anti-DNP secretion in hybridoma 35-12 and plasmacytoma MOPC-315 cells. To further study the mechanism of this suppression, the effect of DNP-MGG on anti-DNP synthesis and cell proliferation was investigated in these cell lines. Cultured tumor cells (1 × 106) were injected ip into syngeneic mice. These mice were then given either 1 mg MGG or 1 mg DNP-MGG. At different days after injection, tumor cells obtained from these mice were assayed for anti-DNP secretion, anti-DNP synthesis, cell proliferation, and tumor cell size. When the anti-DNP secretion was suppressed by DNP-MGG, the intracellular synthesis of anti-DNP, demonstrated by [3H]leucine incorporation into DNP-binding activity, was also suppressed. Simultaneous assays of [3H]thymidine incorporation demonstrated that proliferation was also suppressed. Tumor cells injected ip into mice normally become small nonsecreting cells and later return to preinjection size and secrete antibody. Those cells whose antibody synthesis and proliferation were suppressed by DNP-MGG remained smaller. 相似文献
195.
Cell-free translation of mouse liver mRNA coding for two forms of UDP glucuronosyltransferase 总被引:1,自引:0,他引:1
Mouse liver poly(A) RNA, when translated in vitro, produced two forms of UDP glucuronosyltransferase with molecular weights of approximately 50,000 and 54,000 (designated GTm1 and GTm2, respectively). These forms were identified by antibody prepared against GTm1. The mRNA coding for GTm1 was preferentially increased twofold after treatment of mice with 3-methylcholanthrene, while GTm2 mRNA was unaffected. Phenobarbital, however, increased the translatable levels of the mRNAs coding for both proteins approximately twofold. GTm1 was shown to be glycosylated during translation in the presence of dog pancreatic microsomes. This was reflected by a decrease in mobility of the protein in sodium dodecyl sulfate-polyacrylamide gels as compared to GTm1 translated in the absence of microsomes. Further evidence for glycosylation in vivo was demonstrated by an increase in the mobility of GTm1 immunoadsorbed from microsomes treated with endoglycosidase H. In contrast, GTm2 was unmodified. This apparent difference in the state of glycosylation may reflect a difference in the transmembrane distribution of these two enzyme forms, and hence play an important role in determining the type of aglycone glucuronidated and its route of removal from the cell. 相似文献
196.
摘要 目的:探讨脑缺血大鼠microRNA-126(MiR-126)在脑组织和血浆中表达的动态变化及与细胞凋亡的关系。方法:健康雄性SD大鼠45只随机分为3组,其中3只大鼠不作任何处理,用于检测正常大鼠中MiR-126在脑组织和血浆的表达,剩余大鼠随机分为假手术组和模型组,模型组用线栓法造脑缺血大鼠模型。TTC法检测模型组大鼠脑组织梗死病变用以确定造模是否成功;RT-qPCR检测大鼠造模后1、3、6、9、12、24和48小时脑组织和血浆中MiR-126的动态表达变化;采用苏木精-伊红染色法检测脑组织形态学变化;采用Western blot 方法分析相关凋亡蛋白表达的变化。结果:TTC法和H-E染色结果表明,大鼠脑缺血造模成功,模型组大鼠出现脑组织大面积梗死病变;MiR-126和Caspase-3表达在模型组大鼠脑组织和血浆中随着脑缺血时间的延长其表达水平逐渐提高,24 h到达高峰后,在48 h Mi-R126表达强度又降低,但仍然高于假手术组大鼠水平;Caspase-3在正常对照组和假手术组表达量都较少(P>0.05),其他凋亡蛋白Bax和 STAT3相对表达水平趋势同 Caspase-3相似;而Bcl-2表达水平明显降低,趋势与其他凋亡蛋白相反。结论:MiR-126在脑缺血大鼠脑组织和血浆中表达水平明显升高,而且细胞凋亡明显增加,因此MiR-126可能通过促进细胞凋亡对脑缺血大鼠有保护作用,此研究为脑缺血发病机制和诊断提供更多依据。 相似文献
197.
Aspandiar G. Katki Charles E. Myers 《Biochemical and biophysical research communications》1980,96(1):85-91
A membrane-bound glutathione peroxidase-like activity has been detected in liver and cardiac mitochondrial membrane. This enzyme activity differs from the cytosol and mitochondrial matrix selenium-dependent glutathione peroxidase in that it is membrane bound, sensitive to sonication and triton-X-100, and is unaffected by prolonged feeding of a selenium-free diet. This mitochondrial membrane-bound enzyme activity differs from the glutathione-S-transferases which exhibit glutathione peroxidase activity in that it is capable of utilizing both cumene hydroperoxide and hydrogen peroxide as substrates. Digitonin fractionation studies indicate that this enzyme is not located in either inner or outer mitochondrial membrane but rather within inter-membrane space. This newly described membrane-bound enzyme activity may play an important role in the maintenance of cardiac mitochondrial integrity in that mitochondrial matrix does not contain glutathione peroxidase. 相似文献
198.
Ascorbic acid deficiency and cytochrome P-450 in adult rat hepatocytes in primary monolayer culture.
Adult rat hepatocytes in primary monolayer culture exhibit selective alteration of microsomal constituents and functions during the first hours of incubation ex vivo, including a striking decrease in the concentration of cytochrome P-450. The present studies document that these alterations are due in part to deficiency of l-ascorbate in the cultured cells. The deficiency appears to develop both by loss of the vitamin from the cells during their preparation and by a diminished synthetic capacity for ascorbate. Supplementation of the culture medium with l-ascorbate, at a concentration sufficient to restore intracellular levels of vitamin C to normal, results in maintenance of significantly increased concentrations of cytochromes P-450 and b5. The activity of NADPH cytochrome c reductase similarly is ascorbate-dependent, suggesting that the vitamin plays a role in the formation and/or stabilization of membrane protein or lipid. Microsomal heme metabolism appeared to be unaffected by the presence or absence of ascorbate. 相似文献
199.
Gillian L. Dornan Udit Dalwadi David J. Hamelin Reece M. Hoffmann Calvin K. Yip John E. Burke 《Journal of molecular biology》2018,430(18):3129-3142
Phosphatidylinositol 4-kinase IIIα (PI4KIIIα) is the lipid kinase primarily responsible for generating the lipid phosphatidylinositol 4-phosphate (PI4P) at the plasma membrane, which acts as the substrate for generation of the signaling lipids PIP2 and PIP3. PI4KIIIα forms a large heterotrimeric complex with two regulatory partners, TTC7 and FAM126. We describe using an integrated electron microscopy and hydrogen–deuterium exchange mass spectrometry (HDX-MS) approach to probe the architecture and dynamics of the complex of PI4KIIIα/TTC7/FAM126. HDX-MS reveals that the majority of the PI4KIIIα sequence was protected from exchange in short deuterium pulse experiments, suggesting presence of secondary structure, even in putative unstructured regions. Negative stain electron microscopy reveals the shape and architecture of the full-length complex, revealing an overall dimer of PI4KIIIα/TTC7/FAM126 trimers. HDX-MS reveals conformational changes in the TTC7/FAM126 complex upon binding PI4KIIIα, including both at the direct TTC7-PI4KIIIα interface and at the putative membrane binding surface. Finally, HDX-MS experiments of PI4KIIIα bound to the highly potent and selective inhibitor GSK-A1 compared to that bound to the non-specific inhibitor PIK93 revealed substantial conformational changes throughout an extended region of the kinase domain. Many of these changes were distant from the putative inhibitor binding site, showing a large degree of allosteric conformational changes that occur upon inhibitor binding. Overall, our results reveal novel insight into the regulation of PI4KIIIα by its regulatory proteins TTC7/FAM126, as well as additional dynamic information on how selective inhibition of PI4KIIIα is achieved. 相似文献
200.
R Nossal G H Weiss P K Nandi R E Lippoldt H Edelhoch 《Archives of biochemistry and biophysics》1983,226(2):593-603
Clathrin-coated vesicles obtained from bovine brain have been studied by ultracentrifugation and dynamic light scattering techniques to provide information on their sedimentation and mass distributions and their average diffusion coefficients. "Uncoated" vesicles, obtained by removing the protein coat from coated vesicles, have been similarly characterized. For typical preparations, maximal values of approximately 210 and 95 S are observed for the sedimentation coefficients of coated and uncoated vesicles, respectively. Corresponding values for the average molecular weights, determined from values of average sedimentation and diffusion coefficients, are 49 X 10(6) and 13 X 10(6); values obtained by equilibrium sedimentation are 37.2 X 10(6) and 10.6 X 10(6). In order to obtain these results, some minor modifications of sedimentation and light-scattering techniques have been devised which may have application to other studies of size distributions of large particles. 相似文献