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1.
ObjectiveWe investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs).MethodsCortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.ResultsMdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.ConclusionseEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent. 相似文献
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W. D. Roof H. Q. Fang K. D. Young Jianling Sun & Ry Young 《Molecular microbiology》1997,25(6):1031-1046
slyD encodes a 196 amino acid polypeptide that is a member of the FKBP family of cis–trans peptidyl–prolyl isomerases (PPIases). slyD mutations affect plaque formation by the phage φX174 by blocking the action of the phage lysis protein E. Here we describe the selection of a set of spontaneous slyD mutations conferring resistance to the expression of gene E from a plasmid. These mutations occur disproportionately in residues of SlyD that, based on the structure of the prototype mammalian FKBP12, make ligand contacts with immunosuppressing drug molecules or are conserved in other FKBP proteins. A wide variation in the plating efficiency of φX174 on these E R strains is observed, relative to the parental, indicating that these alleles differ widely in residual SlyD activity. Moreover, it is found that slyD mutations cause significant growth rate defects in Escherichia coli B and C backgrounds. Finally, overexpression of slyD causes filamentation of the host. Thus, among the FKBP genes found in organisms across the evolutionary spectrum, slyD is unique in having three distinct drug-independent phenotypes. 相似文献
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Mapping QTLs and meta-QTLs for two inflorescence architecture traits in multiple maize populations under different watering environments 总被引:1,自引:0,他引:1
Xiaoqiang Zhao Yunling Peng Jinwen Zhang Peng Fang Boyang Wu 《Molecular breeding : new strategies in plant improvement》2017,37(7):91
Drought significantly affects the architectural development of maize inflorescence, which leads to massive losses in grain yield. However, the genetic mechanism for traits involved in inflorescence architecture in different watering environments, remains poorly understood in maize. In this study, 19 QTLs for tassel primary branch number (TBN) and ear number per plant (EN) were detected in 2 F2:3 populations under both well-watered and water-stressed environments by single environment mapping with composite interval mapping (CIM); 11/19 QTLs were detected under water-stressed environments. Moreover, 21 QTLs were identified in the 2 F2:3 populations by joint analysis of all environments with a mixed linear model based on composite interval mapping (MCIM), 11 QTLs were involved in QTL × environment interactions, seven epistatic interactions were identified with additive by additive/dominance effects. Remarkably, 12 stable QTLs (sQTLs) were simultaneously detected by single environment mapping with CIM and joint analysis through MCIM, which were concentrated in ten bins across the chromosomes: 1.05_1.07, 1.08_1.10, 2.01_2.04, 3.01, 4.06, 4.09, 5.06_5.07, 6.05, 7.00, and 7.04 regions. Twenty meta-QTLs (mQTLs) were detected across 19 populations under 51 watering environments using a meta-analysis, and 34 candidate genes were predicted in corresponding mQTLs regions to be involved in the regulation of inflorescence development and drought resistance. Therefore, these results provide valuable information for finding quantitative trait genes and to reveal the genetic mechanisms responsible for TBN and EN under different watering environments. Furthermore, alleles for TBN and EN provide useful targets for marker-assisted selection to generate high-yielding maize varieties. 相似文献
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We have used diffusion and branching process methods to investigate fixation rates, probabilities of survival per generation, and times to fixation of mutant genes under different selection methods incorporating individual and family information. Diffusion approximations fit well to simulated results even for large selection coefficients. Methods that give much weight to family information, such as BLUP evaluation which is widely used in animal breeding, reduce fixation rates of mutant genes because of the reduced effective population sizes. In general, it is observed that even mutants with relatively small heterozygous effects (say 0.1 phenotypic standard deviation) are practically ‘safe’ (i.e. their probability of loss from one generation to the next is smaller than, say, 10%) after just a few generations, typically less than 10. For methods of selection with larger effective size, such as within-family selection, the mutant is ‘safe’ in the population somewhat earlier but eventual fixation takes a longer time. Finally we evaluate the amount by which the use of marker assisted selection reduces the fixation probability of newly arisen mutants. 相似文献
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Hui-juan Zhu Lin-jie Wang Xiang-qing Wang Hui Pan Nai-shi Li Hong-bo Yang Ming Jin Bao-xia Zang Feng-ying Gong 《Cytotechnology》2015,67(5):885-892
Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been demonstrated to prevent steroid-induced avascular necrosis of femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic differentiation induced by steroid. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1 preadipocytes and cell viability greatly decreased in a dose and time dependent manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and triglyceride content in adipocytes by 21.3 % (2.13 ± 0.36 vs 2.71 ± 0.40, P < 0.01) and 22.6 % (1.33 ± 0.07 vs 1.72 ± 0.07, P < 0.01) on days 8 following the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone-sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55-fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity. 相似文献
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Mitochondrial DNA (mtDNA) copy number in peripheral blood has been suggested as risk modifier in various types of cancer. However, its influence on melanoma risk is unclear. We evaluated the association between mtDNA copy number in peripheral blood and melanoma risk in 500 melanoma cases and 500 healthy controls from an ongoing melanoma study. The mtDNA copy number was measured using real-time polymerase chain reaction. Overall, mean mtDNA copy number was significantly higher in cases than in controls (1.15 vs 0.99, P<0.001). Increased mtDNA copy number was associated with a 1.45-fold increased risk of melanoma (95% confidence interval: 1.12-1.97). Significant joint effects between mtDNA copy number and variables related to pigmentation and history of sunlight exposure were observed. This study supports an association between increased mtDNA copy number and melanoma risk that is independent on the known melanoma risk factors (pigmentation and history of sunlight exposure). 相似文献