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Yiqun Wang Masja M. Van Oort Minghui Yao Dick J. Van der Horst Kees W. Rodenburg 《Biological trace element research》2011,142(3):735-747
Chromium picolinate (CrPic) has been indicated to activate glucose transporter 4 (GLUT4) trafficking to the plasma membrane
(PM) to enhance glucose uptake in 3T3-L1 adipocytes. In skeletal and heart muscle cells, insulin directs the intracellular
trafficking of the fatty acid translocase/CD36 to induce the uptake of cellular long-chain fatty acid (LCFA). The current
study describes the effects of CrPic and insulin on the translocation of CD36 from intracellular storage pools to the PM in
3T3-L1 adipocytes in comparison with that of GLUT4. Immunofluorescence microscopy and immunoblotting revealed that both CD36
and GLUT4 were expressed and primarily located intracellularly in 3T3-L1 adipocytes. Upon insulin or CrPic stimulation, PM
expression of CD36 increased in a similar manner as that for GLUT4; the CrPic-stimulated PM expression was less strong than
that of insulin. The increase in PM localization for these two proteins by insulin paralleled LCFA ([1-14C]palmitate) or [3H]deoxyglucose uptake in 3T3-L1 adipocytes. The induction of the PM expression of GLUT4, but not CD36, or substrate uptake
by insulin and CrPic appears to be additive in adipocytes. Furthermore, wortmannin completely inhibited the insulin-stimulated
translocation of GLUT4 or CD36 and prevented the increased uptake of glucose or LCFA in these cells. Taken together, for the
first time, these findings suggest that both insulin and CrPic induce CD36 translocation to the PM in 3T3-L1 adipocytes and
that their translocation-inducing effects are not additive. The signaling pathway inducing the translocations is different,
apparently resulting in a differential activity of CD36. 相似文献
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135.
Yiqun Zhang W. Armand Guiguemde Martina Sigal Fangyi Zhu Michele C. Connelly Solomon Nwaka R. Kiplin Guy 《Bioorganic & medicinal chemistry》2010,18(7):2756-2766
Malaria is endemic in tropical and subtropical regions of Africa, Asia, and the Americas. The increasing prevalence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new antimalarial drugs. In this light, novel scaffolds to which the parasite has not been exposed are of particular interest. Recently, workers at the Swiss Tropical Institute discovered two novel 4-oxo-3-carboxyl quinolones active against the intra-erythrocytic stages of P. falciparum while carrying out rationally directed low-throughput screening of potential antimalarial agents as part of an effort directed by the World Health Organization. Here we report the design, synthesis, and preliminary pharmacologic characterization of a series of analogues of 4-oxo-3-carboxyl quinolones. These studies indicate that the series has good potential for preclinical development. 相似文献
136.
Probe-based fluorescence melting curve analysis (FMCA) is a powerful tool for mutation detection based on melting temperature generated by thermal denaturation of the probe-target hybrid. Nevertheless, the color multiplexing, probe design, and cross-platform compatibility remain to be limited by using existing probe chemistries. We hereby explored two dual-labeled, self-quenched probes, TaqMan and shared-stem molecular beacons, in their ability to conduct FMCA. Both probes could be directly used for FMCA and readily integrated with closed-tube amplicon hybridization under asymmetric PCR conditions. Improved flexibility of FMCA by using these probes was illustrated in three representative applications of FMCA: mutation scanning, mutation identification and mutation genotyping, all of which achieved improved color-multiplexing with easy probe design and versatile probe combination and all were validated with a large number of real clinical samples. The universal cross-platform compatibility of these probes-based FMCA was also demonstrated by a 4-color mutation genotyping assay performed on five different real-time PCR instruments. The dual-labeled, self-quenched probes offered unprecedented combined advantage of enhanced multiplexing, improved flexibility in probe design, and expanded cross-platform compatibility, which would substantially improve FMCA in mutation detection of various applications. 相似文献
137.
Jing Lv Jianjian Qi Qiuxiang Shi Di Shen Shengping Zhang Guangjin Shao Hang Li Zhanyong Sun Yiqun Weng Yi Shang Xingfang Gu Xixiang Li Xiaoguo Zhu Jinzhe Zhang Robbert van Treuren Willem van Dooijeweert Zhonghua Zhang Sanwen Huang 《PloS one》2012,7(10)
Knowing the extent and structure of genetic variation in germplasm collections is essential for the conservation and utilization of biodiversity in cultivated plants. Cucumber is the fourth most important vegetable crop worldwide and is a model system for other Cucurbitaceae, a family that also includes melon, watermelon, pumpkin and squash. Previous isozyme studies revealed a low genetic diversity in cucumber, but detailed insights into the crop''s genetic structure and diversity are largely missing. We have fingerprinted 3,342 accessions from the Chinese, Dutch and U.S. cucumber collections with 23 highly polymorphic Simple Sequence Repeat (SSR) markers evenly distributed in the genome. The data reveal three distinct populations, largely corresponding to three geographic regions. Population 1 corresponds to germplasm from China, except for the unique semi-wild landraces found in Xishuangbanna in Southwest China and East Asia; population 2 to Europe, America, and Central and West Asia; and population 3 to India and Xishuangbanna. Admixtures were also detected, reflecting hybridization and migration events between the populations. The genetic background of the Indian germplasm is heterogeneous, indicating that the Indian cucumbers maintain a large proportion of the genetic diversity and that only a small fraction was introduced to other parts of the world. Subsequently, we defined a core collection consisting of 115 accessions and capturing over 77% of the SSR alleles. Insight into the genetic structure of cucumber will help developing appropriate conservation strategies and provides a basis for population-level genome sequencing in cucumber. 相似文献
138.
Liu J Ouyang M Jiang J Mu P Wu J Yang Q Zhang C Xu W Wang L Huen MS Deng Y 《Mutation research》2012,741(1-2):70-75
Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS. 相似文献
139.
S Li J Qian Y Yang W Zhao J Dai JX Bei JN Foo PJ McLaren Z Li J Yang F Shen L Liu J Yang S Li S Pan Y Wang W Li X Zhai B Zhou L Shi X Chen M Chu Y Yan J Wang S Cheng J Shen W Jia J Liu J Yang Z Wen A Li Y Zhang G Zhang X Luo H Qin M Chen H Wang L Jin D Lin H Shen L He PI de Bakker H Wang YX Zeng M Wu Z Hu Y Shi J Liu W Zhou 《PLoS genetics》2012,8(7):e1002791
Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10−19) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10−8), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10−4; rs455804: OR = 0.84, P = 6.92×10−3). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC. 相似文献