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32.
Identification of acyl coenzyme A:monoacylglycerol acyltransferase 3, an intestinal specific enzyme implicated in dietary fat absorption 总被引:3,自引:0,他引:3
Cheng D Nelson TC Chen J Walker SG Wardwell-Swanson J Meegalla R Taub R Billheimer JT Ramaker M Feder JN 《The Journal of biological chemistry》2003,278(16):13611-13614
Acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol using 2-monoacylglycerol and fatty acyl coenzyme A. This enzymatic reaction is believed to be an essential and rate-limiting step for the absorption of fat in the small intestine. Although the first MGAT-encoding cDNA, designated MGAT1, has been recently isolated, it is not expressed in the small intestine and hence cannot account for the high intestinal MGAT enzyme activity that is important for the physiology of fat absorption. In the current study, we report the identification of a novel MGAT, designated MGAT3, and present evidence that it fulfills the criteria to be the elusive intestinal MGAT. MGAT3 encodes a approximately 36-kDa transmembrane protein that is highly homologous to MGAT1 and -2. In humans, expression of MGAT3 is restricted to gastrointestinal tract with the highest level found in the ileum. At the cellular level, recombinant MGAT3 is localized to the endoplasmic reticulum. Recombinant MGAT3 enzyme activity produced in insect Sf9 cells selectively acylates 2-monoacylglycerol with higher efficiency than other stereoisomers. The molecular identification of MGAT3 will facilitate the evaluation of using intestinal MGAT as a potential point of intervention for antiobesity therapies. 相似文献
33.
Suzanne E Wahrle Aarti R Shah Anne M Fagan Scott Smemo John SK Kauwe Andrew Grupe Anthony Hinrichs Kevin Mayo Hong Jiang Leon J Thal Alison M Goate David M Holtzman 《Molecular neurodegeneration》2007,2(1):1-9
Background
Animal studies suggest that brain apolipoprotein E (apoE) levels influence amyloid-β (Aβ) deposition and thus risk for Alzheimer's disease (AD). We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1) in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF) apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs).Results
In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r2 = 0.93, p < 0.01). In contrast, CSF apoE levels in different individuals varied widely (coefficient of variation = 46%). CSF apoE levels did not vary according to AD status, APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r2 = 0.05, p = 0.003). We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported.Conclusion
We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set. 相似文献34.
Gipson Joe Anto Sureka Sekaran Bojarajan Perumal Natarajan Ramar R Vaitheeswaran SK Karthikeyan 《Reports of Practical Oncology and Radiotherapy》2022,27(1):161
BackgroundThe objective of this study is to determine the impact of intensity modulated proton therapty (IMPT) optimization techniques on the proton dose comparison of commercially available magnetic resonance for calculating attenuation (MRCA T) images, a synthetic computed tomography CT (sCT) based on magnetic resonance imaging (MRI) scan against the CT images and find out the optimization technique which creates plans with the least dose differences against the regular CT image sets.Material and methodsRegular CT data sets and sCT image sets were obtained for 10 prostate patients for the study. Six plans were created using six distinct IMPT optimization techniques including multi-field optimization (MFO), single field uniform dose (SFUD) optimization, and robust optimization (RO) in CT image sets. These plans were copied to MRCA T, sCT datasets and doses were computed. Doses from CT and MRCA T data sets were compared for each patient using 2D dose distribution display, dose volume histograms (DVH), homogeneity index (HI), conformation number (CN) and 3D gamma analysis. A two tailed t-test was conducted on HI and CN with 5% significance level with a null hypothesis for CT and sCT image sets.ResultsAnalysis of ten CT and sCT image sets with different IMPT optimization techniques shows that a few of the techniques show significant differences between plans for a few evaluation parameters. Isodose lines, DVH, HI, CN and t-test analysis shows that robust optimizations with 2% range error incorporated results in plans, when re-computed in sCT image sets results in the least dose differences against CT plans compared to other optimization techniques. The second best optimization technique with the least dose differences was robust optimization with 5% range error.ConclusionThis study affirmatively demonstrates the impact of IMPT optimization techniques on synthetic CT image sets dose comparison against CT images and determines the robust optimization with 2% range error as the optimization technique which gives the least dose difference when compared to CT plans. 相似文献
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Transduction of Well-Differentiated Airway Epithelium by Recombinant Adeno-Associated Virus Is Limited by Vector Entry
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Robert Bals Weidong Xiao Nianli Sang Daniel J. Weiner Rupalie L. Meegalla James M. Wilson 《Journal of virology》1999,73(7):6085-6088
The limitations of adeno-associated virus (AAV)-mediated vectors for lung-directed gene transfer were investigated by using differentiated human respiratory epithelium in air-liquid interface cultures. Transduction efficiency was high in undifferentiated cells and was enhanced in well-differentiated cells after basolateral application of the vector or after apical application following disruption of tight junctions or pretreatment of the cultures with glycosidases. These results indicate that transduction of airway epithelia by AAV vectors is limited by entry and reinforce the importance of a physical barrier on the airway surface. 相似文献
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Kenneth J. Wilson Carl R. Illig Jinsheng Chen Mark J. Wall Shelley K. Ballentine Renee L. DesJarlais Yanmin Chen Carsten Schubert Robert Donatelli Ioanna Petrounia Carl S. Crysler Christopher J. Molloy Margery A. Chaikin Carl L. Manthey Mark R. Player Bruce E. Tomczuk Sanath K. Meegalla 《Bioorganic & medicinal chemistry letters》2010,20(13):3925-3929
During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity. 相似文献
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Meegalla SK Doller D Liu R Sha D Lee Y Soll RM Wisnewski N Silver GM Dhanoa D 《Bioorganic & medicinal chemistry letters》2006,16(6):1702-1706
A number of fluorinated 1-aryl-tetrahydrocyclopentapyrazoles were synthesized and their insecticidal activity was evaluated. Some of the fluorinated compounds had significant insecticidal properties. 相似文献
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Meegalla SK Wall MJ Chen J Wilson KJ Ballentine SK Desjarlais RL Schubert C Crysler CS Chen Y Molloy CJ Chaikin MA Manthey CL Player MR Tomczuk BE Illig CR 《Bioorganic & medicinal chemistry letters》2008,18(12):3632-3637
An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions. 相似文献
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HANDE GURER-ORHAN HILMI ORHAN SIBEL SUZEN M. ORHAN PÜSKÜLLÜ ERDEM BUYUKBINGOL 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):241-247
New, except 1d, melatonin analogue benzimidazole derivatives were synthesized and characterized in the present study. The potential role of melatonin as an antioxidant by scavenging and detoxifying ROS raised the possibility that compounds that are analogous to melatonin can also be used for their antioxidant properties. Therefore the antioxidant effects of the newly synthesized compounds were investigated in vitro by means of their inhibitory effect on hydrogen peroxide-induced erythrocyte membrane lipid peroxidation (EMLP) and on various erythrocyte antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT) and glucose-6-phosphate dehydrogenase (G6PD). The synthesized benzimidazole derivatives showed remarkable antioxidant activity in vitro in the H2O2-induced EMLP system. Furthermore their effects on various antioxidant enzymes are discussed and evaluated from the perspective of structure- activity relationships. 相似文献
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MAGDALENA WITEK PIOTR NOWICKI EWA B. ŚLIWIŃSKA PIOTR SKÓRKA JOSEF SETTELE KARSTEN SCHÖNROGGE MICHAL WOYCIECHOWSKI 《Ecological Entomology》2010,35(5):557-564
1. Phengaris butterflies are obligatory social parasites of Myrmica ants. Early research suggested that there is a different Myrmica host species for each of the five European Phengaris social parasites, but more recent studies have shown that this was an oversimplification. 2. The pattern of host ant specificity within a Phengaris teleius metapopulation from southern Poland is reported. A combination of studying the frequency distribution of Phengaris occurrence and morphometrics on adult butterflies were used to test whether use of different host species is reflected in larval development. 3. Phengaris teleius larvae were found to survive in colonies of four Myrmica species: M. scabrinodis, M. rubra, M. ruginodis, and M. rugulosa. Myrmica scabrinodis was the most abundant species under the host plant but the percentage of infested nests was similar to other host ant species at two sites and lower in comparison to nests of M. rubra and M. ruginodis at the other two sites. Morphometric measurements of adult butterflies reared by wild colonies of M. scabrinodis and M. ruginodis showed that wing size and number of wing spots were slightly greater for adults eclosing from nests of M. ruginodis. 4. Our results suggest that P. teleius in the populations studied is less specialised than previously suggested. The results are consistent with the hypothesis that P. teleius is expected to be the least specific of the European Phengaris species, as it has the largest and best defended fourth‐instar caterpillars and, as a predatory species, it spends less time in the central larval chambers of the host colonies. The fact that individuals reared by M. ruginodis had wider hind wings may suggest that P. teleius had better access to resources in M. ruginodis than in M. scabrinodis colonies. 相似文献