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201.
An NSP4-dependant mechanism by which rotavirus impairs lactase enzymatic activity in brush border of human enterocyte-like Caco-2 cells 总被引:1,自引:0,他引:1
Beau I Cotte-Laffitte J Géniteau-Legendre M Estes MK Servin AL 《Cellular microbiology》2007,9(9):2254-2266
Lactase-phlorizin hydrolase (LPH, EC 3.2.1.23-62) is a brush border membrane (BBM)-associated enzyme in intestinal cells that hydrolyse lactose, the most important sugar in milk. Impairing in lactase activity during rotavirus infection has been described in diseased infants but the mechanism by which the functional lesion occurs remains unknown. We undertook a study to elucidate whether rotavirus impairs the lactase enzymatic activity in BBM of human enterocyte cells. In this study we use cultured human intestinal fully differentiated enterocyte-like Caco-2 cells to demonstrate how the lactase enzymatic activity at BBM is significantly decreased in rhesus monkey rotavirus (RRV)-infected cells. We found that the decrease in enzyme activity is not dependent of the Ca(2+)- and cAMP-dependent signalling events triggered by the virus. The LPH biosynthesis, stability, and expression of the protein at the BBM of infected cells were not modified. We provide evidence that in RRV-infected cells the kinetic of lactase enzymatic activity present at the BBM was modified. Both BBM(control) and BBM(RRV) have identical K(m) values, but hydrolyse the substrate at different rates. Thus, the BBM(RRV) exhibits almost a 1.5-fold decreased V(max) than that of BBM(control) and is therefore enzymatically less active than the latter. Our study demonstrate conclusively that the impairment of lactase enzymatic activity at the BBM of the enterocyte-like Caco-2 cells observed during rotavirus infection results from an inhibitory action of the secreted non-structural rotavirus protein NSP4. 相似文献
202.
Solignac M Zhang L Mougel F Li B Vautrin D Monnerot M Cornuet JM Worley KC Weinstock GM Gibbs RA 《Genome biology》2007,8(3):403
Two independent genome projects for the honey bee, a microsatellite linkage map and a genome sequence assembly, interactively produced an almost complete organization of the euchromatic genome. Assembly 4.0 now includes 626 scaffolds that were ordered and oriented into chromosomes according to the framework provided by the third-generation linkage map (AmelMap3). Each construct was used to control the quality of the other. The co-linearity of markers in the sequence and the map is almost perfect and argues in favor of the high quality of both. 相似文献
203.
Gonçalves Renata C. Carvalho Celso Carneiro Michels Monique Abatti Mariane R. Manfredini Andressa Silva Milena C. Dominguini Diogo Steckert Amanda Mina Francielle Streck Emílio Budni Josiane Dal-Pizzol Felipe 《Neurochemical research》2022,47(3):613-621
Neurochemical Research - Critical illness encompasses a wide spectrum of life-threatening clinical conditions requiring intensive care. Our objective was to evaluate cognitive, inflammatory and... 相似文献
204.
Lijs Beke Cenk Kig Joannes?T. M. Linders Shannah Boens An Boeckx Erika van Heerde Marc Parade An De Bondt Ilse Van den Wyngaert Tarig Bashir Souichi Ogata Lieven Meerpoel Aleyde Van Eynde Christopher?N. Johnson Monique Beullens Dirk Brehmer Mathieu Bollen 《Bioscience reports》2015,35(6)
Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and is overexpressed in many cancer cells. The oncogenic function of MELK is attributed to its capacity to disable critical cell-cycle checkpoints and reduce replication stress. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing. In the present study, we have explored the biological function of MELK using MELK-T1, a novel and selective small-molecule inhibitor. Strikingly, MELK-T1 triggered a rapid and proteasome-dependent degradation of the MELK protein. Treatment of MCF-7 (Michigan Cancer Foundation-7) breast adenocarcinoma cells with MELK-T1 induced the accumulation of stalled replication forks and double-strand breaks that culminated in a replicative senescence phenotype. This phenotype correlated with a rapid and long-lasting ataxia telangiectasia-mutated (ATM) activation and phosphorylation of checkpoint kinase 2 (CHK2). Furthermore, MELK-T1 induced a strong phosphorylation of p53 (cellular tumour antigen p53), a prolonged up-regulation of p21 (cyclin-dependent kinase inhibitor 1) and a down-regulation of FOXM1 (Forkhead Box M1) target genes. Our data indicate that MELK is a key stimulator of proliferation by its ability to increase the threshold for DNA-damage tolerance (DDT). Thus, targeting MELK by the inhibition of both its catalytic activity and its protein stability might sensitize tumours to DNA-damaging agents or radiation therapy by lowering the DNA-damage threshold. 相似文献
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Zhi Liu Esther C. Leng Kannan Gunasekaran Martin Pentony Min Shen Monique Howard Janelle Stoops Kathy Manchulenko Vladimir Razinkov Hua Liu William Fanslow Zhonghua Hu Nancy Sun Haruki Hasegawa Rutilio Clark Ian N. Foltz Wei Yan 《The Journal of biological chemistry》2015,290(12):7535-7562
Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies. 相似文献
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209.
Diverse functional outcomes of Plasmodium falciparum ligation of EPCR: potential implications for malarial pathogenesis 下载免费PDF全文
Mark R. Gillrie Marion Avril Andrew J. Brazier Shevaun P. Davis Monique F. Stins Joseph D. Smith May Ho 《Cellular microbiology》2015,17(12):1883-1899
Plasmodium falciparum‐infected erythrocytes (IRBC) expressing the domain cassettes (DC) 8 and 13 of the cytoadherent ligand P. falciparum erythrocyte membrane protein 1 adhere to the endothelial protein C receptor (EPCR). By interfering with EPCR anti‐coagulant and pro‐endothelial barrier functions, IRBC adhesion could promote coagulation and vascular permeability that contribute to the pathogenesis of cerebral malaria. In this study, we examined the adhesion of DC8‐ and DC13‐expressing parasite lines to endothelial cells from different microvasculature, and the consequences of EPCR engagement on endothelial cell function. We found that IRBC from IT4var19 (DC8) and IT4var07 (DC13) parasite lines adhered to human brain, lung and dermal endothelial cells under shear stress. However, the relative contribution of EPCR to parasite cytoadherence on different types of endothelial cell varied. We also observed divergent functional outcomes for DC8 cysteine‐rich interdomain region (CIDR)α1.1 and DC13 CIDRα1.4 domains. IT4var07 CIDRα1.4 inhibited generation of activated protein C (APC) on lung and dermal endothelial cells and blocked the APC–EPCR binding interaction on brain endothelial cells. IT4var19 CIDRα1.1 inhibited thrombin‐induced endothelial barrier dysfunction in lung endothelial cells, whereas IT4var07 CIDRα1.4 inhibited the protective effect of APC on thrombin‐induced permeability. Overall, these findings reveal a much greater complexity of how CIDRα1‐expressing parasites may modulate malaria pathogenesis through EPCR adhesion. 相似文献