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41.
Nonglucosylated oligosaccharides are transferred to protein in MI8-5 Chinese hamster ovary cells 总被引:3,自引:2,他引:1
A CHO mutant MI8-5 was found to synthesize Man9-GlcNAc2-P-P-dolichol rather
than Glc3Man9GlcNAc2-P-P-dolichol as the oligosaccharide-lipid intermediate
in N-glycosylation of proteins. MI8-5 cells were incubated with labeled
mevalonate, and the prenol was found to be dolichol. The mannose-labeled
oligosaccharide released from oligosaccharide-lipid of MI8-5 cells was
analyzed by HPLC and alpha-mannosidase treatment, and the data were
consistent with a structure of Man9GlcNAc2. In addition, MI8-5 cells did
not incorporate radioactivity into oligosaccharide- lipid during an
incubation with tritiated galactose, again consistent with MI8-5 cells
synthesizing an unglucosylated oligosaccharide-lipid. MI8-5 cells had
parental levels of glucosylphosphoryldolichol synthase activity. However,
in two different assays, MI8-5 cells lacked dolichol-
P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase activity. MI8-5 cells
were found to synthesize glucosylated oligosaccharide after they were
transfected with Saccharomyces cerevisiae ALG 6, the gene for
dolichol-P-Glc:Man9GlcNAc2-P-P-dolichol glucosyltransferase. MI8-5 cells
were found to incorporate mannose into protein 2-fold slower than parental
cells and to approximately a 2-fold lesser extent.
相似文献
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Duijnisveld BJ Bigot A Beenakker KG Portilho DM Raz V van der Heide HJ Visser CP Chaouch S Mamchaoui K Westendorp RG Mouly V Butler-Browne GS Nelissen RG Maier AB 《Arthritis research & therapy》2011,13(6):R207-10
Introduction
Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.Methods
As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.Results
After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.Conclusions
In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate. 相似文献44.
Andrew B. Yeatts Daniel T. ChoquetteJohn P. Fisher 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Mesenchymal stem cells (MSCs) are a promising cell source for bone and cartilage tissue engineering as they can be easily isolated from the body and differentiated into osteoblasts and chondrocytes. A cell based tissue engineering strategy using MSCs often involves the culture of these cells on three-dimensional scaffolds; however the size of these scaffolds and the cell population they can support can be restricted in traditional static culture. Thus dynamic culture in bioreactor systems provides a promising means to culture and differentiate MSCs in vitro.Scope of review
This review seeks to characterize key MSC differentiation signaling pathways and provides evidence as to how dynamic culture is augmenting these pathways. Following an overview of dynamic culture systems, discussion will be provided on how these systems can effectively modify and maintain important culture parameters including oxygen content and shear stress. Literature is reviewed for both a highlight of key signaling pathways and evidence for regulation of these signaling pathways via dynamic culture systems.Major conclusions
The ability to understand how these culture systems are affecting MSC signaling pathways could lead to a shear or oxygen regime to direct stem cell differentiation. In this way the efficacy of in vitro culture and differentiation of MSCs on three-dimensional scaffolds could be greatly increased.General significance
Bioreactor systems have the ability to control many key differentiation stimuli including mechanical stress and oxygen content. The further integration of cell signaling investigations within dynamic culture systems will lead to a quicker realization of the promise of tissue engineering and regenerative medicine. This article is part of a Special Issue entitled Biochemistry of Stem Cells. 相似文献45.
Jorit JL Meesters Ann Bremander Stefan Bergman Ingemar F Petersson Aleksandra Turkiewicz Martin Englund 《Arthritis research & therapy》2014,16(5)
Introduction
Depression is frequent in ankylosing spondylitis (AS) patients. However, epidemiological data about the potential increase in risk are lacking. This study compares the rate of doctor-diagnosed depression in a well defined cohort of AS patients to the general population seeking care.Methods
The Skåne Healthcare Register comprises healthcare data of each resident in Region Skåne, Sweden (population 1.2 million), including ICD-10 diagnoses. Using physician coded consultation data from years 1999 to 2011, we calculated depression consultation rates for all AS patients. We obtained standardized depression-rate ratios by dividing the observed depression rate in AS patients by the expected rate based on the corresponding age- and sex-specific rates of depression in the general population seeking care. A ratio >1 equals a higher rate of depression among AS patients.Results
The AS cohort consisted of 1738 subjects (65% men) with a mean age of 54 years. The reference population consisted of 967,012 subjects. During the 13-year observation period 10% (n = 172) of the AS cohort had a doctor-diagnosed depression compared to 6% (n = 105) to be expected. The standardized estimate of depression-rate ratio was 1.81 (95% confidence interval 1.44 to 2.24) in women men and 1.49 (1.20 to 1.89) in men.Conclusions
The rate of doctor-diagnosed depression is increased about 80% in female and 50% in male AS patients. Future challenges are to timely identify and treat the AS patients who suffer from depression. 相似文献46.
Background
The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage. 相似文献47.
48.
We provide an overview of terrestrial animal translocations carried out for conservation purposes in Britain, summarising what has been achieved in recent decades and discussing the issues raised by this approach to conservation. In the last 40 years, at least nine species have been reintroduced following extinction in Britain (or at least one country within Britain), including five birds, one mammal, one amphibian and two invertebrates. Many more species have been translocated within Britain to establish additional populations in order to improve conservation status. We discuss the guidelines and protocols used to assess translocation projects in Britain, notably the IUCN guidelines, most recently revised in 2013. We also discuss the likely use of species translocations in future and suggest that, in our increasingly fragmented landscapes, they will have an important role to play in conservation restoration, especially for animals with limited mobility. Moving species around is a complex undertaking and our understanding of the inherent risks involved, including the risks from disease, has improved significantly in recent years. Conservation translocations should be considered in the context of species recovery targets and high standards should be maintained so that disease risks and other potentially negative impacts are minimised. 相似文献
49.
50.
C Allard V Desgagné J Patenaude M Lacroix L Guillemette MC Battista M Doyon J Ménard JL Ardilouze P Perron L Bouchard MF Hivert 《Epigenetics》2015,10(4):342-351
Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10−11; N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. 相似文献