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排序方式: 共有338条查询结果,搜索用时 31 毫秒
71.
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Yang Y Zhang Y Cuevas S Villar VA Escano C D Asico L Yu P Grandy DK Felder RA Armando I Jose PA 《Free radical biology & medicine》2012,53(3):437-446
The dopamine D(2) receptor (D(2)R) regulates renal reactive oxygen species (ROS) production, and impaired D(2)R function results in ROS-dependent hypertension. Paraoxonase 2 (PON2), which belongs to the paraoxonase gene family, is expressed in various tissues, acting to protect against cellular oxidative stress. We hypothesized that PON2 may be involved in preventing excessive renal ROS production and thus may contribute to maintenance of normal blood pressure. Moreover, D(2)R may decrease ROS production, in part, through regulation of PON2. D(2)R colocalized with PON2 in the brush border of mouse renal proximal tubules. Renal PON2 protein was decreased (-33±6%) in D(2)(-/-) relative to D(2)(+/+) mice. Renal subcapsular infusion of PON2 siRNA decreased PON2 protein expression (-55%), increased renal oxidative stress (2.2-fold), associated with increased renal NADPH oxidase expression (Nox1, 1.9-fold; Nox2, 2.9-fold; and Nox4, 1.6-fold) and activity (1.9-fold), and elevated arterial blood pressure (systolic, 134±5 vs 93±6mmHg; diastolic, 97±4 vs 65±7mmHg; mean 113±4 vs 75±7mmHg). To determine the relevance of the PON2 and D(2)R interaction in humans, we studied human renal proximal tubule cells. Both D(2)R and PON2 were found in nonlipid and lipid rafts and physically interacted with each other. Treatment of these cells with the D(2)R/D(3)R agonist quinpirole (1μM, 24h) decreased ROS production (-35±6%), associated with decreased NADPH oxidase activity (-32±3%) and expression of Nox2 (-41±7%) and Nox4 (-47±8%) protein, and increased expression of PON2 mRNA (2.1-fold) and protein (1.6-fold) at 24h. Silencing PON2 (siRNA, 10nM, 48h) not only partially prevented the quinpirole-induced decrease in ROS production by 36%, but also increased basal ROS production (1.3-fold), which was associated with an increase in NADPH oxidase activity (1.4-fold) and expression of Nox2 (2.1-fold) and Nox4 (1.8-fold) protein. Inhibition of NADPH oxidase with diphenylene iodonium (10μM/30 min) inhibited the increase in ROS production caused by PON2 silencing. Our results suggest that renal PON2 is involved in the inhibition of renal NADPH oxidase activity and ROS production and contributes to the maintenance of normal blood pressure. PON2 is positively regulated by D(2)R and may, in part, mediate the inhibitory effect of renal D(2)R on NADPH oxidase activity and ROS production. 相似文献
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Andrew Ramsay Luis E. Cuevas Catherine J. F. Mundy Carl-Michael Nathanson Petros Chirambo Russell Dacombe S. Bertel Squire Felix M. L. Salaniponi Sera Munthali 《PloS one》2009,4(11)
Background
To quantify the likely impact of recent WHO policy recommendations regarding smear microscopy and the introduction of appropriate low-cost fluorescence microscopy on a) case detection and b) laboratory workload.Methodology/Principal Findings
An audit of the laboratory register in an urban hospital, Lilongwe, Malawi, and the application of a simple modelling framework. The adoption of the new definition of a smear-positive case could directly increase case detection by up to 28%. Examining Ziehl-Neelsen (ZN) sputum smears for up to 10 minutes before declaring them negative has previously been shown to increase case detection (over and above that gained by the adoption of the new case definition) by 70% compared with examination times in routine practice. Three times the number of staff would be required to adequately examine the current workload of smears using ZN microscopy. Through implementing new policy recommendations and LED-based fluorescence microscopy the current laboratory staff complement could investigate the same number of patients, examining auramine-stained smears to an extent that is equivalent to a 10 minutes ZN smear examination.Conclusions/Significance
Combined implementation of the new WHO recommendations on smear microscopy and LED-based fluorescence microscopy could result in substantial increases in smear positive case-detection using existing human resources and minimal additional equipment. 相似文献75.
Gul W Hammond NL Yousaf M Bowling JJ Schinazi RF Wirtz SS de Castro Andrews G Cuevas C Hamann MT 《Bioorganic & medicinal chemistry》2006,14(24):8495-8505
As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of new semisynthetic products was evaluated for biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic diseases, and cancer. Compound 4 showed potent activity against HIV-1 (EC50 0.47 μg/mL), compound 19 proved to possess remarkable activity against Mycobacterium intracellulare with an IC50 and MIC value of 0.15 and 0.31 μg/mL, while compounds 4 and 17 possessed anti-leishmanial activity with IC50 values of 0.1 and 0.4 μg/mL, respectively. Compounds 16 and 17 showed antimalarial activity with EC50 values of 230 and 240 ng/mL, respectively, and compound 14 exhibited an EC50 of 0.05 μM against the Leukemia cell line K-562. 相似文献
76.
Putrescine accumulation confers drought tolerance in transgenic Arabidopsis plants over-expressing the homologous Arginine decarboxylase 2 gene 总被引:1,自引:0,他引:1
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Terry Disz Sajia Akhter Daniel Cuevas Robert Olson Ross Overbeek Veronika Vonstein Rick Stevens Robert A Edwards 《BMC bioinformatics》2010,11(1):319
Background
The SEED integrates many publicly available genome sequences into a single resource. The database contains accurate and up-to-date annotations based on the subsystems concept that leverages clustering between genomes and other clues to accurately and efficiently annotate microbial genomes. The backend is used as the foundation for many genome annotation tools, such as the Rapid Annotation using Subsystems Technology (RAST) server for whole genome annotation, the metagenomics RAST server for random community genome annotations, and the annotation clearinghouse for exchanging annotations from different resources. In addition to a web user interface, the SEED also provides Web services based API for programmatic access to the data in the SEED, allowing the development of third-party tools and mash-ups. 相似文献79.
80.
Nina Korzeniewski Rolando Cuevas Anette Duensing Stefan Duensing 《Molecular biology of the cell》2010,21(22):3942-3951
The centrosome is the major microtubule-organizing center of most mammalian cells and consists of a pair of centrioles embedded in pericentriolar material. Before mitosis, the two centrioles duplicate and two new daughter centrioles form adjacent to each preexisting maternal centriole. After initiation of daughter centriole synthesis, the procentrioles elongate in a process that is poorly understood. Here, we show that inhibition of cellular proteolysis by Z-L3VS or MG132 induces abnormal elongation of daughter centrioles to approximately 4 times their normal length. This activity of Z-L3VS or MG132 was found to correlate with inhibition of intracellular protease-mediated substrate cleavage. Using a small interfering RNA screen, we identified a total of nine gene products that either attenuated (seven) or promoted (two) abnormal Z-L3VS–induced daughter centriole elongation. Our hits included known regulators of centriole length, including CPAP and CP110, but, interestingly, several proteins involved in microtubule stability and anchoring as well as centrosome cohesion. This suggests that nonproteasomal functions, specifically inhibition of cellular proteases, may play an important and underappreciated role in the regulation of centriole elongation. They also highlight the complexity of daughter centriole length control and provide a framework for future studies to dissect the molecular details of this process. 相似文献