619 research outputs found
Occurrence of a new hematoside in the kidney of guinea pig
AbstractWe have isolated a new hematoside from guinea pig kidney. Like the usual hematoside (II3NeuAc-LacCer), isolated from human erythrocytes, this new hematoside contained glucose, galactose, and N-acetylneuraminic acid in an equimolar proportion. By thin-layer chromatography (TLC), however, it migrated faster than the usual hematoside. After mild alkaline hydrolysis the TLC mobility of this ganglioside bacame identical to that of the usual hematoside. The sialic acid in this ganglioside was susceptible to Clostridial neuraminidase. Based on TLC mobility and the results of periodate oxidation, the sialic acid of the new hematoside was identified as 9-O-acetyl-N-acetylneuraminic acid. Therefore, the structure of this new hematoside is 9-O-Ac-NeuAcα2→3Galβ1→4GLcβ1→1′Cer
Linear Structure of the Oligosaccharide Chains in α_1-Protease Inhibitor Isolated from Human Plasma
Two glycopeptides present in equal amounts were isolated from a pronase digest of alpha1-protease inhibitor of human plasma by gel filtration on Sephadex G-50 and chromatography on DEAE-cellulose. The carbohydrate side chains in both glycopeptides are linked through asparaginyl residues. The glycopeptides were digested sequentially with specific glycosidases; and after each step, the released sugars as well as the composition of the residual peptides were determined. The linear structures of these glycopeptides deduced from these data are shown below. Based on the total carbohydrate content of the intact protein and with these structural data, it is postulated that 4 oligosaccharide units are attached to 1 molecule of the protein; 2 of these were represented as in Equation 1, the other 2 as in Equation 2
Specificity of mouse GM2 activator protein and beta-N-acetylhexosaminidases A and B. Similarities and differences with their human counterparts in the catabolism of GM2.
Tay-Sachs disease, an inborn lysosomal disease featuring a buildup of GM2 in the brain, is caused by a deficiency of β-hexosaminidase A (Hex A) or GM2activator. Of the two human lysosomal Hex isozymes, only Hex A, not Hex B, cleaves GM2 in the presence of GM2activator. In contrast, mouse Hex B has been reported to be more active than Hex A in cleaving GM2 (Burg, J., Banerjee, A., Conzelmann, E., and Sandhoff, K. (1983) Hoppe Seyler's Z. Physiol. Chem. 364, 821–829). In two independent studies, mice with the targeted disruption of the Hexa gene did not display the severe buildup of brain GM2 or the concomitant abnormal behavioral manifestations seen in human Tay-Sachs patients. The results of these two studies were suggested to be attributed to the reported GM2 degrading activity of mouse Hex B. To clarify the specificity of mouse Hex A and Hex B and to better understand the observed results of the mouse model of Tay-Sachs disease, we have purified mouse liver Hex A and Hex B and also prepared the recombinant mouse GM2 activator. Contrary to the findings of Burget al., we found that the specificities of mouse Hex A and Hex B toward the catabolism of GM2 were not different from the corresponding human Hex isozymes. Mouse Hex A, but not Hex B, hydrolyzes GM2 in the presence of GM2activator, whereas GM2 is refractory to mouse Hex B with or without GM2 activator. Importantly, we found that, in contrast to human GM2 activator, mouse GM2activator could effectively stimulate the hydrolysis of GA2by mouse Hex A and to a much lesser extent also by Hex B. These results provide clear evidence on the existence of an alternative pathway for GM2 catabolism in mice by converting GM2 to GA2 and subsequently to lactosylceramide. They also provide the explanation for the lack of excessive GM2 accumulation in the Hexa gene-disrupted mice
Ethnic differences in compulsory admissions for psychiatric disorders in the UK: a systematic review and meta-analysis
Glucosylceramide synthase upregulates MDR1 expression in the regulation of cancer drug resistance through cSrc and β-catenin signaling
<p>Abstract</p> <p>Background</p> <p>Drug resistance is the outcome of multiple-gene interactions in cancer cells under stress of anticancer agents. <it>MDR1 </it>overexpression is most commonly detected in drug-resistant cancers and accompanied with other gene alterations including enhanced glucosylceramide synthase (GCS). <it>MDR1 </it>encodes for P-glycoprotein that extrudes anticancer drugs. Polymorphisms of <it>MDR1 </it>disrupt the effects of P-glycoprotein antagonists and limit the success of drug resistance reversal in clinical trials. GCS converts ceramide to glucosylceramide, reducing the impact of ceramide-induced apoptosis and increasing glycosphingolipid (GSL) synthesis. Understanding the molecular mechanisms underlying <it>MDR1 </it>overexpression and how it interacts with GCS may find effective approaches to reverse drug resistance.</p> <p>Results</p> <p><it>MDR1 </it>and <it>GCS </it>were coincidently overexpressed in drug-resistant breast, ovary, cervical and colon cancer cells; silencing <it>GCS </it>using a novel mixed-backbone oligonucleotide (MBO-asGCS) sensitized these four drug-resistant cell lines to doxorubicin. This sensitization was correlated with the decreased <it>MDR1 </it>expression and the increased doxorubicin accumulation. Doxorubicin treatment induced GCS and <it>MDR1 </it>expression in tumors, but MBO-asGCS treatment eliminated "in-vivo" growth of drug-resistant tumor (NCI/ADR-RES). MBO-asGCS suppressed the expression of <it>MDR1 </it>with GCS and sensitized NCI/ADR-RES tumor to doxorubicin. The expression of P-glycoprotein and the function of its drug efflux of tumors were decreased by 4 and 8 times after MBO-asGCS treatment, even though this treatment did not have a significant effect on P-glycoprotein in normal small intestine. GCS transient transfection induced <it>MDR1 </it>overexpression and increased P-glycoprotein efflux in dose-dependent fashion in OVCAR-8 cancer cells. GSL profiling, silencing of globotriaosylceramide synthase and assessment of signaling pathway indicated that GCS transfection significantly increased globo series GSLs (globotriaosylceramide Gb3, globotetraosylceramide Gb4) on GSL-enriched microdomain (GEM), activated cSrc kinase, decreased β-catenin phosphorylation, and increased nuclear β-catenin. These consequently increased <it>MDR1 </it>promoter activation and its expression. Conversely, MBO-asGCS treatments decreased globo series GSLs (Gb3, Gb4), cSrc kinase and nuclear β-catenin, and suppressed <it>MDR-1 </it>expression in dose-dependent pattern.</p> <p>Conclusion</p> <p>This study demonstrates, for the first time, that GCS upregulates <it>MDR1 </it>expression modulating drug resistance of cancer. GSLs, in particular globo series GSLs mediate gene expression of <it>MDR1 </it>through cSrc and β-catenin signaling pathway.</p
Co-Overexpression of Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Adversely Affects the Postoperative Survival in Non-small Cell Lung Cancer
IntroductionCyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 have been found to be overexpressed in non-small cell lung cancer (NSCLC). The aim of this study was to investigate the expression profiles of COX-2 and mPGES-1 and their correlation with the clinical characteristics and survival outcomes in patients with resected NSCLC.Methods/ResultsSeventy-nine paired adjacent normal-tumor matched samples were prospectively procured from patients undergoing surgery for NSCLC. The protein levels of COX-2 and mPGES-1 were assessed by Western blot analysis. Overexpression in the tumor sample was defined as more than twofold increase in protein expression compared with the corresponding adjacent normal tissue. Co-overexpression of COX-2 and mPGES-1 were further confirmed by immunohistochemistry. COX-2 was overexpressed in 58% and mPGES-1 in 70% of the tumor samples (p < 0.0001). Co-overexpression of mPGES-1 and COX-2 was noted in 43%, and they were unrelated to each other (p = 0.232). Co-overexpression of both proteins was significantly associated with less tumor differentiation (p = 0.046), tumor size larger than 5 cm (p = 0.038), and worse survival status during the follow-up (p = 0.036). Multivariate analysis showed that in addition to overall stage, co-overexpression of both proteins adversely affected the overall (hazard ratio, 2.40; p = 0.045) and disease-free survivals (hazard ratio, 2.27; p = 0.029).ConclusionsOverexpression of either COX-2 or mPGES-1 is common but unrelated in NSCLC. Co-overexpression of both COX-2 and mPGES-1 adversely affects postoperative overall and disease-free survivals
Two different sialidases, KDN-sialidase and regular sialidase in the starfish Asterina pectinifera
An earthquake slip zone is a magnetic recorder
International audienceDuring an earthquake, the physical and the chemical transformations along a slip zone lead to an intense deformation within the gouge layer of a mature fault zone. Because the gouge contains ferromagnetic minerals, it has the capacity to behave as a magnetic recorder during an earthquake. This constitutes a conceivable way to identify earthquakes slip zones. In this paper, we investigate the magnetic record of the Chelungpu fault gouge that hosts the principal slip zone of the Chi-Chi earthquake (Mw 7.6, 1999, Taiwan) using Taiwan Chelungpu-fault Drilling Project core samples. Rock magnetic investigation pinpoints the location of the Chi-Chi mm-thick principal slip zone within the 16-cm thick gouge at ~1 km depth. A modern magnetic dipole of Earth magnetic field is recovered throughout this gouge but not in the wall rocks nor in the two other adjacent fault zones. This magnetic record resides essentially in two magnetic minerals; magnetite in the principal slip zone, and neoformed goethite elsewhere in the gouge. We propose a model where magnetic record: 1) is preserved during inter-seismic time, 2) is erased during co-seismic time and 3) is imprinted during post-seismic time when fluids cooled down. We suggest that the identification of a stable magnetic record carried by neoformed goethite may be a signature of friction-heating process in seismic slip zone
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