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1.
Ai‐Xin Song Chen‐Jie Zhou Xiao Guan Kong‐Hung Sze Hong‐Yu Hu 《Protein science : a publication of the Protein Society》2010,19(5):1104-1109
DC‐UbP/UBTD2 is a ubiquitin (Ub) domain‐containing protein first identified from dendritic cells, and is implicated in ubiquitination pathway. The solution structure and backbone dynamics of the C‐terminal Ub‐like (UbL) domain were elucidated in our previous work. To further understand the biological function of DC‐UbP, we then solved the solution structure of the N‐terminal domain of DC‐UbP (DC‐UbP_N) and studied its Ub binding properties by NMR techniques. The results show that DC‐UbP_N holds a novel structural fold and acts as a Ub‐binding domain (UBD) but with low affinity. This implies that the DC‐UbP protein, composing of a combination of both UbL and UBD domains, might play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells. 相似文献
2.
S A Magder G T Daughters J Hung E L Alderman N B Ingels 《European journal of applied physiology and occupational physiology》1987,56(4):467-473
The purpose of this study was to measure the changes and rates of adaptation of left ventricular volumes at the onset of exercise. Eight asymptomatic subjects, in whom intramyocardial markers had been implanted 3-6 years previously during aortocoronary bypass surgery, exercised in the supine position at a constant workload of 73.6 W for 5 min. Six also exercised first at 16.4 W, and then against a workload which progressively increased by 8.2 W every 15 s. Cardiac volumes were measured by computer assisted analysis of the motion of the implanted markers. In the constant workload test, cardiac output increased rapidly from 5.7 +/- 1 min-1 to 10.3 +/- 1.9 1 min-1 by 2 min and then increased more slowly to 10.8 +/- 2.0 1 min-1 by 5 min. The cardiac output increase was mainly due to an increase in heart rate from 68 +/- 12 beats min-1 to 120 +/- 16 beats min-1 with minimal changes in stroke volume. The time constant for the early increase in cardiac output was 45s and for heart rate, 35s. With progressively increasing workloads, there was an almost linear increase of heart rate and cardiac output, but these increased at a slower rate than during the early phase of the constant load exercise test. In conclusion: rapid changes in cardiac output during supine exercise were produced by changes in heart rate; changes in stroke volume provided minor adjustments to cardiac output; the end-diastolic volume was almost constant. 相似文献
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4.
Cytotoxicity of the redox cycling compound diquat in isolated hepatocytes: involvement of hydrogen peroxide and transition metals 总被引:1,自引:0,他引:1
Diquat is a hepatotoxin whose toxicity in vivo and in vitro is mediated by redox cycling and greatly enhanced by pretreatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. The mechanism by which redox cycling mediates diquat cytotoxicity is unclear, however. Here, we have attempted to examine the roles of three potential products of redox cycling, namely superoxide anion radical (O2-.), hydrogen peroxide (H2O2), and hydroxyl radical (.OH), in the toxicity of diquat to BCNU-treated isolated hepatocytes. Addition of high concentrations of catalase, but not superoxide dismutase, to the incubations provided some protection against the toxic effect of diquat, but much better protection was observed when catalase was added in combination with the iron chelator desferrioxamine. Addition of desferrioxamine alone also provided considerable protection, whereas the addition of copper ions enhanced diquat cytotoxicity. Taken together, these results indicate that both H2O2 and the transition metals iron and copper could play major roles in the cytotoxicity of diquat. The role of O2-. remains less clear, however, but studies with diethylenetriaminepentaacetic acid indicate that O2-. is unlikely to significantly contribute to the reduction of Fe3+ to Fe2+. The hydroxyl radical or a related species seems the most likely ultimate toxic product of the H2O2/Fe2+ interaction, but hydroxyl radical scavengers afforded only minimal protection. 相似文献
5.
Increased efflux rather than oxidation is the mechanism of glutathione depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 总被引:2,自引:0,他引:2
D Di Monte M S Sandy M T Smith 《Biochemical and biophysical research communications》1987,148(1):153-160
Incubation of isolated hepatocytes in the presence of either the parkinsonian-inducing compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or its putative toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) led to a depletion of intracellular reduced glutathione (GSH), which was mostly recovered as glutathione disulfide (GSSG). However, both MPTP- and MPP+-induced glutathione perturbances were relatively unaffected by the prior inhibition of glutathione reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), suggesting that intracellular oxidation was not the major mechanism involved in the GSH loss. Inclusion of cystine in the incubation mixtures revealed a time-dependent formation of cysteinyl glutathione (CySSG), indicating that an increased efflux was mostly responsible for the MPTP- and MPP+-induced GSH depletion. Therefore, the measurement of GSSG, which is apparently formed extracellularly, was not associated with oxidative stress. 相似文献
6.
The mutagenic potencies of 3 purine analogs were determined in the ad-3 forward-mutation test in growing cultures of heterokaryon 59 (H-59), a nucleotide excision repair-deficient (uvs-2/uvs-2) 2-component heterokaryon of Neurospora crassa. Two N-hydroxylaminopurines, 2-amino-6-N-hydroxylaminopurine (AHA) and 6-N-hydroxylaminopurine (HAP), were potent and strong mutagens, respectively, whereas 2-aminopurine (AP) was a moderate mutagen. Dose-response curves showed that AHA and HAP were about equally mutagenic at low doses but that AHA was more mutagenic than HAP at high doses. Comparison of these results in H-59 with our earlier results in heterokaryon 12 (H-12) of N. crassa, which is identical to H-59 except for being DNA-repair-proficient (uvs-2+/uvs-2+), shows that the defect in nucleotide excision repair due to uvs-2 has little or no effect on the mutagenic potencies of these 3 purine analogs. Therefore, the nucleotide excision-repair pathway in N. crassa that is deficient in H-59 does not appear to have a major role in the repair of pre-mutational lesions induced by these 3 purine analogs. On the other hand, based on the controls of these experiments, the frequency of spontaneous ad-3 mutants was 4 greater in H-59 than in H-12. This result suggests that the nucleotide excision-repair pathway in N. crassa that is inactivated by the uvs-2 mutation has a major role in the repair of lesions that would lead to spontaneous mutation at the ad-3+ region if they were not repaired. 相似文献
7.
8.
An in-vivo measurement and analysis of viscoelastic properties of the spinal cord of cats 总被引:6,自引:0,他引:6
An in-vivo experimental technique was employed to determine the linear and nonlinear characteristics of viscoelastic properties of the spinal cord of anesthetized cats. The stress relaxation and recovery curves were reproducible in a group of cat experiments. The data of linear viscoelastic properties were used to develop a power law model with Boltzmann's convolution integral. The model was capable of predicting a prolonged stress relaxation and recovery curve. For larger deformation, the results were quantified using a nonlinear analysis of viscoelastic response of the spinal cord under the uniaxial experiment. 相似文献
9.
I A Cotgreave M Weis M Berggren M S Sandy P W Moldéus 《Journal of biochemical and biophysical methods》1988,16(4):247-254
The derivatisation of intact rat hepatocytes with monobromobimane resulted in rapid labelling of accessible protein thiols in several subcellular fractions. The derivatisation procedure did not cause acute cytotoxicity, nor did it alter the buoyant densities of the fractions or their gross protein compositions. Quantitation of the fluorescence irreversibly associated with the fractions demonstrated considerable intracellular heterogeneity in this pool of thiols. Values were highest in cytosol (ca. 90 nmol/mg protein), intermediate in microsomes (ca. 65 nmol/mg protein) and mitochondria (ca. 45 nmol/mg protein) and lowest in a crude fraction containing both nuclei and plasma membrane (ca. 35 nmol/mg protein). Similar values were obtained from microsomes and cytosol derivatised after fractionation but there were significant increases of ca. 100% in corresponding values from isolated mitochondria and the nuclear/plasma membrane fraction. These results are discussed in terms of the dynamic fluxes in monobromobimane protein thiols during fractionation and the applicability of this noninvasive method to studies of the mechanism(s) of toxicity of reactive xenobiotics and the role(s) of protein thiols in normal cellular function. 相似文献
10.
Formaldehyde was tested for its killing and mutagenic activities in the ad-3 forward-mutation test in Neurospora crassa. The test was conducted in 3 two-component heterokaryons (dikaryons) of N. crassa in order to determine the effect of the uvs-2 allele, which causes a defect in nucleotide excision repair, on formaldehyde-induced killing and the induction of ad-3 mutants. These dikaryons were homokaryotic for uvs-2+ (H-12), homokaryotic for usv-2 (H-59), and heterokaryotic for uvs-2 (H-71). Formaldehyde induced killing and ad-3 mutants in H-12, but the presence of uvs-2 in the homokaryotic state (H-59) resulted in a 9-fold increase in killing and a 40-fold increase in the induction of ad-3 mutants. This increased sensitivity to formaldehyde-induced killing and mutation conferred by uvs-2 in the homokaryotic state (H-59 vs. H-12) is similar to that noted by others in Escherichia coli. Salmonella typhimurium and Saccharomyces cerevisiae. The dikaryon heterokaryotic for uvs-2 (H-71) has the same sensitivity to formaldehyde-induced ad-3 mutation as H-12, indicating that uvs-2 is recessive to uvs-2+. 相似文献