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991.
Tong Shen Ye-Hong Kuang Charles R. Ashby Jr Yu Lei Angel Chen Ying Zhou Xiang Chen Amit K. Tiwari Elizabeth Hopper-Borge Jiangyong Ouyang Zhe-Sheng Chen 《PloS one》2009,4(10)
Background
One of the major mechanisms that could produce resistance to antineoplastic drugs in cancer cells is the ATP binding cassette (ABC) transporters. The ABC transporters can significantly decrease the intracellular concentration of antineoplastic drugs by increasing their efflux, thereby lowering the cytotoxic activity of antineoplastic drugs. One of these transporters, the multiple resistant protein 7 (MRP7, ABCC10), has recently been shown to produce resistance to antineoplastic drugs by increasing the efflux of paclitaxel. In this study, we examined the effects of BCR-Abl tyrosine kinase inhibitors imatinib, nilotinib and dasatinib on the activity and expression of MRP7 in HEK293 cells transfected with MRP7, designated HEK-MRP7-2.Methodology and/or Principal Findings
We report for the first time that imatinib and nilotinib reversed MRP7-mediated multidrug resistance. Our MTT assay results indicated that MRP7 expression in HEK-MRP7-2 cells was not significantly altered by incubation with 5 µM of imatinib or nilotinib for up to 72 hours. In addition, imatinib and nilotinib (1-5 µM) produced a significant concentration-dependent reversal of MRP7-mediated multidrug resistance by enhancing the sensitivity of HEK-MRP7-2 cells to paclitaxel and vincristine. Imatinib and nilotinib, at 5 µM, significantly increased the accumulation of [3H]-paclitaxel in HEK-MRP7-2 cells. The incubation of the HEK-MRP7-2 cells with imatinib or nilotinib (5 µM) also significantly inhibited the efflux of paclitaxel.Conclusions
Imatinib and nilotinib reverse MRP7-mediated paclitaxel resistance, most likely due to their inhibition of the efflux of paclitaxel via MRP7. These findings suggest that imatinib or nilotinib, in combination with other antineoplastic drugs, may be useful in the treatment of certain resistant cancers. 相似文献992.
Attribution of biological robustness to the specific structural properties of a regulatory network is an important yet unsolved problem in systems biology. It is widely believed that the topological characteristics of a biological control network largely determine its dynamic behavior, yet the actual mechanism is still poorly understood. Here, we define a novel structural feature of biological networks, termed ‘regulation entropy’, to quantitatively assess the influence of network topology on the robustness of the systems. Using the cell-cycle control networks of the budding yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) as examples, we first demonstrate the correlation of this quantity with the dynamic stability of biological control networks, and then we establish a significant association between this quantity and the structural stability of the networks. And we further substantiate the generality of this approach with a broad spectrum of biological and random networks. We conclude that the regulation entropy is an effective order parameter in evaluating the robustness of biological control networks. Our work suggests a novel connection between the topological feature and the dynamic property of biological regulatory networks. 相似文献
993.
Lianying Jiao Songying Ouyang Neil Shaw Gaojie Song Yingang Feng Fengfeng Niu Weicheng Qiu Hongtao Zhu Li-Wei Hung Xiaobing Zuo V. Eleonora Shtykova Ping Zhu Yu-Hui Dong Ruxiang Xu Zhi-Jie Liu 《蛋白质与细胞》2014,5(8):616
Uch37 is a de-ubiquitinating enzyme that is activated by Rpn13 and involved in the proteasomal degradation of proteins. The full-length Uch37 was shown to exhibit low iso-peptidase activity and is thought to be auto-inhibited. Structural comparisons revealed that within a homodimer of Uch37, each of the catalytic domains was blocking the other’s ubiquitin (Ub)-binding site. This blockage likely prevented Ub from entering the active site of Uch37 and might form the basis of auto-inhibition. To understand the mode of auto-inhibition clearly and shed light on the activation mechanism of Uch37 by Rpn13, we investigated the Uch37-Rpn13 complex using a combination of mutagenesis, biochemical, NMR, and smallangle X-ray scattering (SAXS) techniques. Our results also proved that Uch37 oligomerized in solution and had very low activity against the fluorogenic substrate ubiquitin-7-amino-4-methylcoumarin (Ub-AMC) of de-ubiquitinating enzymes. Uch37ΔHb,Hc,KEKE, a truncation removal of the C-terminal extension region (residues 256–329) converted oligomeric Uch37 into a monomeric form that exhibited iso-peptidase activity comparable to that of a truncation-containing the Uch37 catalytic domain only. Wealso demonstrated that Rpn13C (Rpn13 residues 270–407) could disrupt the oligomerization of Uch37 by sequestering Uch37 and forming a Uch37-Rpn13 complex. Uch37 was activated in such a complex, exhibiting 12-fold-higher activity than Uch37 alone. Time-resolved SAXS (TR-SAXS) and FRET experiments supported the proposed mode of auto-inhibition and the activation mechanism of Uch37 by Rpn13. Rpn13 activated Uch37 by forming a 1:1 stoichiometric complex in which the active site of Uch37 was accessible to Ub. 相似文献
994.
Jie Ouyang Xiao-dong Wang Bing Zhao Yu-chun Wang 《Enzyme and microbial technology》2005,36(7):982-988
An internal loop airlift bioreactor with sifter riser (ILABSR) was composed of a bubble column and a draught-tube rolled with 40-mesh sifter that placed 5 cm above the bottom at the center of the column. A 2 L ILABSR was used for the suspension cultivation of Cistanche deserticola cells and its performance was compared with shake flask culture and a bubble column. Under the optimum culture conditions with the air flowrate of 0.075 m3/h and the inoculation size of 4.7%, about one-fifth cells were attached to the sifter draught-tube. PeG content in these cells was 16.3%, which was 104% higher than that of suspension cells. The production of phenylethanoid glycosides reached 0.85 g/L, which was 102 and 4% higher than those cultured in a 2 L bubble column and shake flasks respectively under their optimal culture conditions. 相似文献
995.
996.
Liuzhang Ouyang Wei Chen Jiangwen Liu Michael Felderhoff Hui Wang Min Zhu 《Liver Transplantation》2017,7(19)
Sodium borohydride (NaBH4) is regarded as an excellent hydrogen‐generated material, but its irreversibility of hydrolysis and high cost of regeneration restrict its large‐scale application. In this study a convenient and economical method for NaBH4 regeneration is developed for the first time without hydrides used as starting materials for the reduction process. The real hydrolysis by‐products (NaBO2 · 2H2O and NaBO2 · 4H2O), instead of dehydrated sodium metaborate (NaBO2), are applied for the regeneration of NaBH4 with Mg at room temperature and atmospheric pressure. Therefore, the troublesome heat‐wasting process to obtain NaBO2 using a drying procedure at over 350 °C from NaBO2 · xH2O is omitted. Moreover, the highest regeneration yields of NaBH4 are achieved to date with 68.55% and 64.06% from reaction with NaBO2 · 2H2O and NaBO2 · 4H2O, respectively. The cost of NaBH4 regeneration shows a 34‐fold reduction compared to the previous study that uses MgH2 as the reduction agent, where H2 is obtained from a separate process. Furthermore, the regeneration mechanism of NaBH4 is clarified and the intermediate compound, NaBH3(OH), is successfully observed for the first time during the regeneration process. 相似文献
997.
Tree growth traits and social status affect the wood density of pioneer species in secondary subtropical forest
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Lingxiu Chen Wenhua Xiang Huili Wu Pifeng Lei Shengli Zhang Shuai Ouyang Xiangwen Deng Xi Fang 《Ecology and evolution》2017,7(14):5366-5377
Wood density (WD) is not only an important parameter to estimate aboveground biomass but also an indicator of timber quality and plant adaptation strategies to stressful conditions (i.e., windthrow, pests, and pathogens). This study had three objectives: (1) to compare WD among seven subtropical tree species; (2) to determine how tree growth traits may influence possible differences in WD between the pioneer and shade‐tolerant species; and (3) to examine whether or not WD differs by tree social status (dominant vs. suppressed trees) within species. To do this, 70 trees were destructively harvested. From each tree, disks at different stem heights were obtained and subjected to a method of stem analysis to measure whole tree level WD. The results showed that WD differed significantly among the seven species (p < .001). Their average WD was 0.537 g/cm3, ranging from 0.409 g/cm3 for Choerospondias axillaris to 0.691 g/cm3 for Cyclobalanopsis glauca. The average WD of the four pioneer species (0.497 ± 0.13 g/cm3) was significantly lower (p < .01) than that of the three shade‐tolerant species (0.589 ± 0.12 g/cm3). The WD of the pioneers had a significant positive correlation with their stem diameter at breast height (DBH), tree height (H), and tree age, but WD had a significant negative correlation with relative growth rate (RGR). In contrast, the WD of the shade‐tolerant tree species had no significant relationships with DBH, H, tree age, or RGR. The dominant trees of the pioneer species had a higher WD than the suppressed trees, whereas the shade‐tolerant species had a lower WD for dominant trees than the suppressed trees. However, the differences in WD between dominant and suppressed trees were not significant. Taken together, the results suggest that classifying species into pioneer and shade‐tolerant groups to examine the effects of tree growth traits and social status could improve our understanding of intra‐ and interspecific variation in WD among subtropical tree species. 相似文献
998.
Matthew Dodson Willayat Y. Wani Matthew Redmann Gloria A. Benavides Michelle S. Johnson Xiaosen Ouyang 《Autophagy》2017,13(11):1828-1840
The production of reactive species contributes to the age-dependent accumulation of dysfunctional mitochondria and protein aggregates, all of which are associated with neurodegeneration. A putative mediator of these effects is the lipid peroxidation product 4-hydroxynonenal (4-HNE), which has been shown to inhibit mitochondrial function, and accumulate in the postmortem brains of patients with neurodegenerative diseases. This deterioration in mitochondrial quality could be due to direct effects on mitochondrial proteins, or through perturbation of the macroautophagy/autophagy pathway, which plays an essential role in removing damaged mitochondria. Here, we use a click chemistry-based approach to demonstrate that alkyne-4-HNE can adduct to specific mitochondrial and autophagy-related proteins. Furthermore, we found that at lower concentrations (5–10 μM), 4-HNE activates autophagy, whereas at higher concentrations (15 μM), autophagic flux is inhibited, correlating with the modification of key autophagy proteins at higher concentrations of alkyne-4-HNE. Increasing concentrations of 4-HNE also cause mitochondrial dysfunction by targeting complex V (the ATP synthase) in the electron transport chain, and induce significant changes in mitochondrial fission and fusion protein levels, which results in alterations to mitochondrial network length. Finally, inhibition of autophagy initiation using 3-methyladenine (3MA) also results in a significant decrease in mitochondrial function and network length. These data show that both the mitochondria and autophagy are critical targets of 4-HNE, and that the proteins targeted by 4-HNE may change based on its concentration, persistently driving cellular dysfunction. 相似文献
999.
Hao Yang Yifan Ouyang Hao Ma Hui Cong Chunlin Zhuang Wun-Taai Lok Zhe Wang Xuanli Zhu Yutong Sun Wei Hong Hao Wang 《Bioorganic & medicinal chemistry letters》2017,27(20):4635-4642
Protein arginine methyltransferase 1 (PRMT1) catalyses the methylation of substrate arginine by transferring the methyl group from SAM (S-adenosyl-l-methionine), which leads to the formation of S-adenosyl homocysteine (SAH) and methylated arginine. We have shown previously that the Asp84 on PRMT1 could be a potential inhibitor binding site. In the current study, 28 compounds were designed and synthesized that were predicted to bind the Asp84 and substrate arginine sites together. Among them, 6 compounds were identified as potential PRMT1 inhibitors, and showed strong inhibitory effects on cancer cell lines, especially HepG2. The most potent PRMT1 inhibitor, compound 13d, was selected for molecular dynamic simulations to investigate binding poses. Based on the free energy calculations and structural analysis, we predicted that the ethylenediamine group would tightly bind to Asp84, and the trifluoromethyl group should occupy part of substrate arginine binding site, which is consistent with our original goal. Our results show for the first time that PRMT1 inhibitors can target the Asp84 binding site, which will be helpful for future drug discovery studies. 相似文献
1000.
Pan Li Tiangen Chang Shuoqi Chang Xiang Ouyang Mingnan Qu Qingfeng Song Langtao Xiao Shitou Xia Qiyun Deng Xin-Guang Zhu 《植物学报(英文版)》2018,60(12):1154-1180
A large number of genes related to source, sink,and flow have been identified after decades of research in plant genetics. Unfortunately, these genes have not been effectively utilized in modern crop breeding. This perspective paper aims to examine the reasons behind such a phenomenon and propose a strategy to resolve this situation. Specifically, we first systematically survey the currently cloned genes related to source, sink, and flow;then we discuss three factors hindering effective application of these identified genes, which include the lack of effective methods to identify limiting or critical steps in a signaling network, the misplacement of emphasis on properties, at the leaf, instead of the whole canopy level,and the non-linear complex interaction between source,sink, and flow. Finally, we propose the development of systems models of source, sink and flow, together with a detailed simulation of interactions between them and their surrounding environments, to guide effective use of the identified elements in modern rice breeding. These systems models will contribute directly to the definition of crop ideotype and also identification of critical features and parameters that limit the yield potential in current cultivars. 相似文献