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排序方式: 共有93条查询结果,搜索用时 15 毫秒
1.
Oxysterols direct immune cell migration via EBI2 总被引:1,自引:0,他引:1
Hannedouche S Zhang J Yi T Shen W Nguyen D Pereira JP Guerini D Baumgarten BU Roggo S Wen B Knochenmuss R Noël S Gessier F Kelly LM Vanek M Laurent S Preuss I Miault C Christen I Karuna R Li W Koo DI Suply T Schmedt C Peters EC Falchetto R Katopodis A Spanka C Roy MO Detheux M Chen YA Schultz PG Cho CY Seuwen K Cyster JG Sailer AW 《Nature》2011,475(7357):524-527
Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response. 相似文献
2.
Dawson MA Prinjha RK Dittmann A Giotopoulos G Bantscheff M Chan WI Robson SC Chung CW Hopf C Savitski MM Huthmacher C Gudgin E Lugo D Beinke S Chapman TD Roberts EJ Soden PE Auger KR Mirguet O Doehner K Delwel R Burnett AK Jeffrey P Drewes G Lee K Huntly BJ Kouzarides T 《Nature》2011,478(7370):529-533
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Carsten Lundby Jose A. L. Calbet Paul Robach 《Cellular and molecular life sciences : CMLS》2009,66(22):3615-3623
Hypoxia refers to environmental or clinical settings that potentially threaten tissue oxygen homeostasis. One unique aspect
of skeletal muscle is that, in addition to hypoxia, oxygen balance in this tissue may be further compromised when exercise
is superimposed on hypoxia. This review focuses on the cellular and molecular responses of human skeletal muscle to acute
and chronic hypoxia, with emphasis on physical exercise and training. Based on published work, it is suggested that hypoxia
does not appear to promote angiogenesis or to greatly alter oxidative enzymes in skeletal muscle at rest. Although the HIF-1
pathway in skeletal muscle is still poorly documented, emerging evidence suggests that muscle HIF-1 signaling is only activated
to a minor degree by hypoxia. On the other hand, combining hypoxia with exercise appears to improve some aspects of muscle
O2 transport and/or metabolism. 相似文献
5.
Very large collisions in the asteroid belt could lead temporarily to a substantial increase in the rate of impacts of meteorites on Earth. Orbital simulations predict that fragments from such events may arrive considerably faster than the typical transit times of meteorites falling today, because in some large impacts part of the debris is transferred directly into a resonant orbit with Jupiter. Such an efficient meteorite delivery track, however, has not been verified. Here we report high-sensitivity measurements of noble gases produced by cosmic rays in chromite grains from a unique suite of fossil meteorites preserved in approximately 480 million year old sediments. The transfer times deduced from the noble gases are as short as approximately 10(5) years, and they increase with stratigraphic height in agreement with the estimated duration of sedimentation. These data provide powerful evidence that this unusual meteorite occurrence was the result of a long-lasting rain of meteorites following the destruction of an asteroid, and show that at least one strong resonance in the main asteroid belt can deliver material into the inner Solar System within the short timescales suggested by dynamical models. 相似文献
6.
Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice 总被引:25,自引:0,他引:25
Orsó E Broccardo C Kaminski WE Böttcher A Liebisch G Drobnik W Götz A Chambenoit O Diederich W Langmann T Spruss T Luciani MF Rothe G Lackner KJ Chimini G Schmitz G 《Nature genetics》2000,24(2):192-196
Mutations in the gene encoding ATP-binding cassette transporter 1 ( ABC1) have been reported in Tangier disease (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system (RES) and aberrant cellular lipid trafficking. We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-AI associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed. 相似文献
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The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++ inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and beta-adrenoceptor agonists exert their positive inotropic effects by increasing Isi via the common mediator cAMP. 相似文献
9.
Summary Patterns of restriction fragment length polymorphisms (RFLP) of European Vespinae were more similar within genera than between them. Distance trees were constructed that support the hypothesis of monophyly of the generaVespula andDolichovespula. Within the genusVespula, V. germanica was more closely related toV. rufa than toV. vulgaris. The position of the genusVespa remained uncertain due to the precision limits of the RFLP technique. 相似文献
10.
RIM1alpha is required for presynaptic long-term potentiation. 总被引:8,自引:0,他引:8
Pablo E Castillo Susanne Schoch Frank Schmitz Thomas C Südhof Robert C Malenka 《Nature》2002,415(6869):327-330
Two main forms of long-term potentiation (LTP)-a prominent model for the cellular mechanism of learning and memory-have been distinguished in the mammalian brain. One requires activation of postsynaptic NMDA (N-methyl d-aspartate) receptors, whereas the other, called mossy fibre LTP, has a principal presynaptic component. Mossy fibre LTP is expressed in hippocampal mossy fibre synapses, cerebellar parallel fibre synapses and corticothalamic synapses, where it apparently operates by a mechanism that requires activation of protein kinase A. Thus, presynaptic substrates of protein kinase A are probably essential in mediating this form of long-term synaptic plasticity. Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable. Here we report that mossy fibre LTP in the hippocampus and the cerebellum is abolished in mice lacking RIM1alpha, an active zone protein that binds to Rab3A and that is also a protein kinase A substrate. Our results indicate that the long-term increase in neurotransmitter release during mossy fibre LTP may be mediated by a unitary mechanism that involves the GTP-dependent interaction of Rab3A with RIM1alpha at the interface of synaptic vesicles and the active zone. 相似文献