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131.
Swift LL Zhu MY Kakkad B Jovanovska A Neely MD Valyi-Nagy K Roberts RL Ong DE Jerome WG 《Journal of lipid research》2003,44(10):1841-1849
Microsomal triglyceride transfer protein (MTP) is essential for the assembly of apolipoprotein B-containing lipoproteins. Within the endoplasmic reticulum, it transfers lipid from the membrane to the forming lipoprotein. Recent evidence suggests that it may also function within the Golgi apparatus. To address this hypothesis, we developed a polyclonal antibody to MTP and used it in a series of studies on mouse liver and McArdle-RH7777 (McA) cells. Western blot analysis demonstrated the presence of MTP within mouse hepatic-Golgi apparatus-rich fractions. In addition, in vitro lipid transfer assays demonstrated the presence of triglyceride transfer activity within the Golgi fractions. Immunohistochemical studies with mouse liver demonstrated the presence of MTP within all hepatocytes, but not in nonparenchymal cells. The subcellular location of MTP in McA cells was investigated using confocal microscopy. MTP colocalized with the trans-Golgi network (TGN) 38 and Golgi SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptor) of 28 kDa (GS28), markers for the trans- and cis-Golgi apparatus, respectively. Morphometric analyses indicated that approximately 17% of the MTP signal colocalized with the TGN38, while 33% of the trans-Golgi marker colocalized with the MTP. Approximately 17% of the MTP signal colocalized with the GS28, whereas 53% of the cis-Golgi marker colocalized with the MTP. The results provide unequivocal evidence for the location of MTP within the Golgi apparatus, and further highlight the importance of this organelle in the assembly of lipoproteins. 相似文献
132.
Multi‐isotype antibody responses against the multimeric Salmonella Typhi recombinant hemolysin E antigen 下载免费PDF全文
Eugene Boon Beng Ong Joshua Ignatius Amy Amilda Anthony Ismail Aziah Asma Ismail Theam Soon Lim 《Microbiology and immunology》2015,59(1):43-47
The detection and measurement of different antibody isotypes in the serum provide valuable indicators of the different stages of typhoid infection. Here, the ability of S. Typhi recombinant hemolysin E (HlyE) to detect multi‐isotype antibody responses in sera of patients with typhoid and paratyphoid A was investigated using an indirect antibody immunoassay. Nanogram amounts of HlyE were found to be sufficient for detection of IgG and IgA isotypes and, in a study of individuals' sera (n = 100), the immunoassay was able to distinguish between typhoid and non‐typhoid sera. The overall sensitivity, specificity and efficiency of the ELISA were 70% (39/56), 100% (44/44) and 83% respectively. 相似文献
133.
Keshava Nagalakshmi Zhou Gu Spruill Michelle Ensell Mang Ong Tong-man 《Molecular and cellular biochemistry》2001,222(1-2):69-76
Occupational exposure to beryllium (Be) and Be compounds occurs in a wide range of industrial processes. A large number of workers are potentially exposed to this metal during manufacturing and processing, so there is a concern regarding the potential carcinogenic hazard of Be. Studies were performed to determine the carcinogenic potential of beryllium sulfate (BeSO4) in cultured mammalian cells. BALB/c3T3 cells were treated with varying concentrations of BeSO4 for 72 h and the transformation frequency was determined after 4 weeks of culturing. Concentrations from 50–200 g BeSO4/ml, caused a concentrationdependent increase (9–41 fold) in transformation frequency. Nontransformed BALB/c3T3 cells and cells from transformed foci induced by BeSO4 were injected into both axillary regions of nude mice. All ten Beinduced transformed cell lines injected into nude mice produced fibrosarcomas within 50 days after cell injection. No tumors were found in nude mice receiving nontransformed BALB/c3T3 cells 90 days postinjection. Gene amplification was investigated in Kras, cmyc, cfos, cjun, csis, erbB2 and p53 using differential PCR while random amplified polymorphic DNA fingerprinting was employed to detect genomic instability. Gene amplification was found in Kras and cjun, however no change in gene expression or protein level was observed in any of the genes by Western blotting. Five of the 10 transformed cell lines showed genetic instability using different random primers. In conclusion, these results indicate that BeSO4 is capable of inducing morphological cell transformation in mammalian cells and that transformed cells induced by BeSO4 are potentially tumorigenic. Also, cell transformation induced by BeSO4 may be attributed, in part, to the gene amplification of Kras and cjun and some BeSO4induced transformed cells possess neoplastic potential resulting from genomic instability. 相似文献
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135.
Although it is well established that exocytosis of neurotransmitters and hormones is highly regulated by numerous secretory proteins, such as SNARE proteins, there is an increasing appreciation of the importance of the chemophysical properties and organization of membrane lipids to various aspects of the exocytotic program. Based on amperometric recordings by carbon fiber microelectrodes, we show that deprivation of membrane cholesterol by methyl-β-cyclodextrin not only inhibited the extent of membrane depolarization-induced exocytosis, it also adversely affected the kinetics and quantal size of vesicle fusion in neuroendocrine PC12 cells. In addition, total internal fluorescence microscopy studies revealed that cholesterol depletion impaired vesicle docking and trafficking, which are believed to correlate with the dynamics of exocytosis. Furthermore, we found that free cholesterol is able to directly trigger vesicle fusion, albeit with less potency and slower kinetics as compared to membrane depolarization stimulation. These results underscore the versatile roles of cholesterol in facilitating exocytosis. 相似文献
136.
Yilong Fu Lai-Chun Ong Sudhir H. Ranganath Lin Zheng Irene Kee Wenbo Zhan Sidney Yu Pierce K. H. Chow Chi-Hwa Wang 《PloS one》2016,11(2)
Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. 相似文献
137.
Ong E Suzuki M Belot F Yeh JC Franceschini I Angata K Hindsgaul O Fukuda M 《The Journal of biological chemistry》2002,277(20):18182-18190
The HNK-1 glycan, sulfo-->3GlcAbeta1-->3Galbeta1-->4GlcNAcbeta1-->R, is highly expressed in neuronal cells and apparently plays critical roles in neuronal cell migration and axonal extension. The HNK-1 glycan synthesis is initiated by the addition of beta1,3-linked GlcA to N-acetyllactosamine followed by sulfation of the C-3 position of GlcA. The cDNAs encoding beta1,3-glucuronyltransferase (GlcAT-P) and HNK-1 sulfotransferase (HNK-1ST) have been recently cloned. Among various adhesion molecules, the neural cell adhesion molecule (NCAM) was shown to contain HNK-1 glycan on N-glycans. In the present study, we first demonstrated that NCAM also bears HNK-1 glycan attached to O-glycans when NCAM contains the O-glycan attachment scaffold, muscle-specific domain, and is synthesized in the presence of core 2 beta1,6-N-acetylglucosaminyltransferase, GlcAT-P, and HNK-1ST. Structural analysis of the HNK-1 glycan revealed that the HNK-1 glycan is attached on core 2 branched O-glycans, sulfo-->3GlcAbeta1-->3Galbeta1-->4GlcNAcbeta1-->6(Galbeta1-->3)GalNAc. Using synthetic oligosaccharides as acceptors, we found that GlcAT-P and HNK-1ST almost equally act on oligosaccharides, mimicking N- and O-glycans. By contrast, HNK-1 glycan was much more efficiently added to N-glycans than O-glycans when NCAM was used as an acceptor. These results are consistent with our results showing that HNK-1 glycan is minimally attached to O-glycans of NCAM in fetal brain, heart, and the myoblast cell line, C2C12. These results combined together indicate that HNK-1 glycan can be synthesized on core 2 branched O-glycans but that the HNK-1 glycan is preferentially added on N-glycans over O-glycans of NCAM, probably because N-glycans are extended further than O-glycans attached to NCAM containing the muscle-specific domain. 相似文献
138.
Tryptophan loading enhances sleep quality by increasing the ratio of plasma tryptophan to large neutral amino acids (TRP:LNAA) and consequently synthesis and availability of serotonin in the brain. Alpha-lactalbulmin (A-LAC) is rich in tryptophan and has the highest TRP:LNAA of all protein sources. This pilot study investigated the effect of an evening intake of A-LAC on objective and subjective sleep measures in male subjects without sleep complaints. Ten healthy male university students (aged: 26.9 ± 5.3 years; BMI: 21.7 ± 1.9 kg.m?2) participated in a double-blind, randomized, and placebo-controlled crossover counter-balanced study. Objective (actigraphy) and subjective (sleep log) sleep measures were recorded for two nights after a standardized evening meal supplemented with either A-LAC (20 g) or a placebo of sodium caseinate (20 g) one hour before bedtime. Evening A-LAC intake resulted in increased objective and subjective total sleep time by 12.8% (p = 0.037) and 10.8% (p = 0.013), respectively, compared to placebo. Objective sleep efficiency increased by 7.0% (p = 0.028) following A-LAC with no significant effects for other sleep indices. This pilot study demonstrates the efficacy of evening A-LAC intake on sleep quality in young healthy adults, however further large-scale studies are warranted to confirm the benefit. 相似文献
139.
Rajkumar Dorajoo Ruoying Li Mohammad Kamran Ikram Jianjun Liu Philippe Froguel Jeannette Lee Xueling Sim Rick Twee-Hee Ong Wan Ting Tay Chen Peng Terri L. Young Alexandra I. F. Blakemore Ching Yu Cheng Tin Aung Paul Mitchell Jie Jin Wang Caroline C. Klaver Eric Boerwinkle Ronald Klein David S. Siscovick Richard A. Jensen Vilmundur Gudnason Albert Vernon Smith Yik Ying Teo Tien Yin Wong E-Shyong Tai Chew-Kiat Heng Yechiel Friedlander 《PloS one》2013,8(7)
Introduction
C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods
Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results
Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10−8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions
Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease. 相似文献140.
Liang Cui Yie Hou Lee Yadunanda Kumar Fengguo Xu Kun Lu Eng Eong Ooi Steven R. Tannenbaum Choon Nam Ong 《PLoS neglected tropical diseases》2013,7(8)