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排序方式: 共有159条查询结果,搜索用时 31 毫秒
31.
The oxidative phosphorylation inhibitor DBCT (dibutylchloromethyltin chloride) inhibits state 3 respiration at a concentration less than that which stimulates K+ flux into respiring rat liver mitochondria. Inhibition of ADP-stimulated respiration by DBCT can be reversed or blocked by the dithiol 2,3-dimercaptopropanol. The data are consistent with previous suggestions that DBCT may interact with the ATP synthase via reaction with a dithiol group. The stimulation of K+ influx by DBCT is partially reversed by concentrations of 2-mercaptoethanol which fail to affect the inhibition of state 3 respiration by DBCT. The combination of DBCT plus 2,3-dimercaptopropanol inhibits mitochondrial K+ influx. The inhibitory effect of dicyclohexylcarbodiimide on K+ influx is not expressed in the presence of DBCT. Atractyloside has little effect on K+ influx in the presence or absence of DBCT. The combination of DBCT plus uncoupler induces a net loss of endogenous K+. Consideration is given to the alternative hypotheses that the acceleration of K+ influx by DBCT may involve either a direct link to the energy transduction apparatus, or may occur via separate activation of a passive transport mechanism. 相似文献
32.
Alphonse LeCam Michael M. Gottesman Ira Pastan 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,675(1):94-100
Glycogen synthase (EC 2.4.1.11) activity was studied in cell extracts from wild-type Chinese hamster ovary (CHO) cells and three mutants resistant to cyclic AMP effects on cell shape and cell growth. Based on the capacity of crude extracts to phosphorylate exogenous hisone, two of the mutants appeared to have altered cyclic AMP-dependent protein kinase (EC 2.7.1.37) and one of them had apparently normal amounts of kinase activity. Glycogen synthase activity was present in comparable amounts in wild-type and all three mutant strains in a presumably inactive phosphorylated form since activity was virtually completely dependent upon the presence of glucose 6-phosphate. The enzyme could be partially dephosphorylated by endogenous phosphatases and rephosphorylated by exogenous cyclic AMP-dependent protein kinase. Attempts to find culture conditions (e.g. glucose starvation)_or cell treatment (e.g. insulin) which might activate glycogen synthase in intact cells were unsuccessful. Since glycogen synthase activity present in CHO cells was independent of the level of cyclic AMP-dependent kinase, we conclude that cyclic AMP-dependent protein kinase does not play a critical role in regulating the state of phosphorylation of the synthase. 相似文献
33.
Schütte D Um-Boock A Mensah-Quainoo E Itin P Schmid P Pluschke G 《PLoS neglected tropical diseases》2007,1(1):e2
Background
Buruli ulcer caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic necrotising skin ulcers. The pathogenesis is associated with the cytocidal and immunosuppressive activities of a macrolide toxin. Histopathological hallmark of progressing disease is a poor inflammatory response despite of clusters of extracellular bacilli. While traditionally wide excision of the infected tissue was the standard treatment, provisional WHO guidelines now recommend an eight week pre-treatment with streptomycin and rifampicin.Methodology/Principal Findings
We conducted a detailed immunohistochemical analysis of tissue samples from Buruli patients who received antibiotic treatment. Cellular immune response along with bacterial load and distribution were monitored. We demonstrate that this treatment leads to the development of highly organized cellular infiltration surrounding areas of coagulative necrosis. Diffuse infiltrates, granulomas and dense lymphocyte aggregation close to vessels were observed. Mycobacterial material was primarily located inside mononuclear phagocytes and microcolonies consisting of extracellular rod-shaped mycobacteria were no longer found. In observational studies some patients showed no clinical response to antibiotic treatment. Corresponding to that, one of five lesions analysed presented with huge clusters of rod-shaped bacilli but no signs of infiltration.Conclusions/Significance
Results signify that eight weeks of antibiotic treatment reverses local immunosuppression and leads to an active inflammatory process in different compartments of the skin. Structured leukocyte infiltrates with unique signatures indicative for healing processes developed at the margins of the lesions. It remains to be analysed whether antibiotic resistance of certain strains of M. ulcerans, lacking patient compliance or poor drug quality are responsible for the absent clinical responses in some patients. In future, analysis of local immune responses could serve as a suitable surrogate marker for the efficacy of alternative treatment strategies. 相似文献34.
Jiang X Klimovich V Arunkumar AI Hysinger EB Wang Y Ott RD Guler GD Weiner B Chazin WJ Fanning E 《The EMBO journal》2006,25(23):5516-5526
We report that during activation of the simian virus 40 (SV40) pre-replication complex, SV40 T antigen (Tag) helicase actively loads replication protein A (RPA) on emerging single-stranded DNA (ssDNA). This novel loading process requires physical interaction of Tag origin DNA-binding domain (OBD) with the RPA high-affinity ssDNA-binding domains (RPA70AB). Heteronuclear NMR chemical shift mapping revealed that Tag-OBD binds to RPA70AB at a site distal from the ssDNA-binding sites and that RPA70AB, Tag-OBD, and an 8-nucleotide ssDNA form a stable ternary complex. Intact RPA and Tag also interact stably in the presence of an 8-mer, but Tag dissociates from the complex when RPA binds to longer oligonucleotides. Together, our results imply that an allosteric change in RPA quaternary structure completes the loading reaction. A mechanistic model is proposed in which the ternary complex is a key intermediate that directly couples origin DNA unwinding to RPA loading on emerging ssDNA. 相似文献
35.
36.
Krystosek A 《Histochemistry and cell biology》1999,111(4):265-276
We have tested the specific hypothesis that the pathway of nuclear collapse in apoptosis is governed by the early attack
on active chromatin at spatially restricted nuclear sites. Cell death in PC12 pheochromocytoma cells deprived of serum growth
factors, in HL-60 leukemic cells treated with inhibitors of protein or RNA biosynthesis, and in U937 histiocytic lymphoma
cells exposed to the cytokine tumor necrosis factor alpha showed a common mechanism in the targeting of DNA for degradation.
An incorporation assay with labeled nucleotide revealed an early selective nicking in peripheral nuclear chromatin with concomitant
diminution in the amount of immunoreactive lamin B protein. This was followed by a phase of more extensive cleavages, continued
nuclear protein loss, chromatin collapse, and fragmentation of nuclei. The spatial restriction of early cleavages is similar
to the nicking obtained by the application of exogenous DNase I to fixed nuclei of normal cells and to that obtained in the
activation of the endogenous endonuclease of liver nuclei by Ca2+. These similarities suggest that, in apoptosis, activation of an endonuclease preferentially recognizing a specific chromatin
configuration, such as that of active (DNase I-sensitive) genes, underlies the early spatial demarcation of cleavages.
Accepted: 12 October 1998 相似文献
37.
Alphonse W Wanyonyi Sumesh C Chhabra Gerald Mkoji Udo Eilert Wilson M Njue 《Phytochemistry》2002,59(1):79-84
Solanum aculeastrum Dunal was investigated for the presence of molluscicidal compounds. This led to the isolation of solaculine A, from the root bark in addition to known steroidal alkaloids; solamargine and beta-solamarine from the berries. The structures were elucidated by spectroscopic techniques. Molluscicidal activity of the aqueous extracts of the berries and root bark, and the isolated compounds were investigated. 相似文献
38.
39.
The Upper Paleocene of E-Tademaït and W-Tinrhertis characterized by a new macrofauna and the appearance of Ranikothalia bermudezi. This is followed by Lower Eocene (Lowermost Ilerdian) Nummulites fraasi and N. deserti, in E-Tademaït.We note in relation with the uplifting of Saharo-Nubianshelf a regressive evolution towards the North, where successively later Nummulites species (deserti, globulus, rollandi, gizehensis) appear during the Lower Eocene. 相似文献
40.
Arunkumar AI Klimovich V Jiang X Ott RD Mizoue L Fanning E Chazin WJ 《Nature structural & molecular biology》2005,12(4):332-339
Simian virus 40 (SV40) provides a model system for the study of eukaryotic DNA replication, in which the viral protein, large T antigen (Tag), marshals human proteins to replicate the viral minichromosome. SV40 replication requires interaction of Tag with the host single-stranded DNA-binding protein, replication protein A (hRPA). The C-terminal domain of the hRPA32 subunit (RPA32C) facilitates initiation of replication, but whether it interacts with Tag is not known. Affinity chromatography and NMR revealed physical interaction between hRPA32C and the Tag origin DNA-binding domain, and a structural model of the complex was determined. Point mutations were then designed to reverse charges in the binding sites, resulting in substantially reduced binding affinity. Corresponding mutations introduced into intact hRPA impaired initiation of replication and primosome activity, implying that this interaction has a critical role in assembly and progression of the SV40 replisome. 相似文献