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排序方式: 共有1302条查询结果,搜索用时 15 毫秒
901.
Daval M Diot-Dupuy F Bazin R Hainault I Viollet B Vaulont S Hajduch E Ferré P Foufelle F 《The Journal of biological chemistry》2005,280(26):25250-25257
Despite its importance in terms of energy homeostasis, the role of AMP-activated protein kinase in adipose tissue remains controversial. Initial studies have described an anti-lipolytic role for AMP-activated protein kinase, whereas more recent studies have suggested the converse. Thus we have addressed the role of AMP-activated protein kinase in adipose tissue by modulating AMP-activated protein kinase activity in primary rodent adipocytes using pharmacological activators or by adenoviral expression of dominant negative or constitutively active forms of the kinase. We then studied the effects of AMP-activated protein kinase activity modulation on lipolytic mechanisms. Finally, we analyzed the consequences of a genetic deletion of AMP-activated protein kinase in mouse adipocytes. AMP-activated protein kinase activity in adipocytes is represented mainly by the alpha(1) isoform and is induced by all of the stimuli that increase cAMP in adipocytes, including fasting. When AMP-activated protein kinase activity is increased by 5-aminoimidazole-4-carboxamide-riboside, phenformin, or by the expression of a constitutively active form, isoproterenol-induced lipolysis is strongly reduced. Conversely, when AMP-activated protein kinase activity is decreased either by a dominant negative form or in AMP-activated protein kinase alpha(1) knock-out mice, lipolysis is increased. We present data suggesting that AMP-activated protein kinase acts on hormone-sensitive lipase by blocking its translocation to the lipid droplet. We conclude that, in mature adipocytes, AMP-activated protein kinase activation has a clear anti-lipolytic effect. 相似文献
902.
Expression of the mouse glutathione transferase Alpha 4 (mGSTA4) has been studied during hepatocyte isolation and in cultured hepatocytes. Transient mGSTA4 induction during liver disruption correlated to strong oxidative stress and induction of the Jun N-terminal kinase (JNK) pathway. Similarly, tumor necrosis factor alpha induced both JNK phosphorylation and mGSTA4 expression while specific JNK inhibitor JNKI1 prevented these two events and JNK activator anisomycin strongly induced mGSTA4 expression. We also found that endogenous JNK and mGSTA4 co-immunoprecipitate. A second mGSTA4 induction occurred 2 days after cell seeding concomitantly to DNA replication and was prevented by treatment with mitogen-activated protein kinase (MEK) inhibitor U0126. Our data demonstrate that mGSTA4 is strongly increased during oxidative stress possibly via JNK pathway and during proliferation via MEK/extracellular signal-regulated kinase pathway, and suggest that mGSTA4 might be an endogenous regulator of JNK activity by direct binding. 相似文献
903.
Berthier-Vergnes O Bermond F Flacher V Massacrier C Schmitt D Péguet-Navarro J 《FEBS letters》2005,579(17):3660-3668
Dendritic cells (DC) play a central role in immunity/tolerance decision, depending on their activation/maturation state. TNF-alpha is largely produced in the skin under inflammatory conditions. However, it still remains to be defined how TNF-alpha modulates the activation status of human LC, the most specialized DC controlling skin immunity. Here, we reported that fresh immature LC, highly purified from healthy human skin and exposed for two days to TNF-alpha under serum-free conditions, expressed up-regulated level of co-stimulatory molecules (CD40, CD54, CD86), maturation markers (CD83, DC-LAMP), CCR7 lymph node homing receptor, and down-regulated Langerin level, in a dose-dependent manner. This mature phenotype is closely associated with enhanced LC allostimulatory capacity. Furthermore, TNF-alpha significantly increased the number of viable LC and decreased their spontaneous apoptosis. More importantly, TNF-alpha induced LC to produce both IFN-gamma-inducible-protein IP-10/CXCL10, a Th1-attracting chemokine and IL-12 p40. Bioactive IL-12 p70 was never detected, even after additional CD40 stimulus. The results implicate LC as an effective target through which TNF-alpha may up- or down-regulate the inflammatory skin reactions. 相似文献
904.
Are spatial memories strengthened in the human hippocampus during slow wave sleep? 总被引:16,自引:0,他引:16
Peigneux P Laureys S Fuchs S Collette F Perrin F Reggers J Phillips C Degueldre C Del Fiore G Aerts J Luxen A Maquet P 《Neuron》2004,44(3):535-545
In rats, the firing sequences observed in hippocampal ensembles during spatial learning are replayed during subsequent sleep, suggesting a role for posttraining sleep periods in the offline processing of spatial memories. Here, using regional cerebral blood flow measurements, we show that, in humans, hippocampal areas that are activated during route learning in a virtual town are likewise activated during subsequent slow wave sleep. Most importantly, we found that the amount of hippocampal activity expressed during slow wave sleep positively correlates with the improvement of performance in route retrieval on the next day. These findings suggest that learning-dependent modulation in hippocampal activity during human sleep reflects the offline processing of recent episodic and spatial memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance. 相似文献
905.
Van Rossum F Bonnin I Fenart S Pauwels M Petit D Saumitou-Laprade P 《Molecular ecology》2004,13(10):2959-2967
Arabidopsis halleri, a close wild relative of A. thaliana, is a clonal, insect-pollinated herb tolerant to heavy metals (Zn, Pd, Cd) and a hyperaccumulator of Zn and Cd. It is of particular interest in the study of evolutionary processes and phytoremediation. However, little is known about its population gene flow patterns and the structure of its genetic diversity. We used five microsatellite loci to investigate the genetic structure at a fine spatial scale (10 cm to 500 m) in a metallicolous population of A. halleri. We also studied the contributions made by clonal propagation and sexual reproduction (seed and pollen dispersal) to the genetic patterns. Clonal diversity was high (D(G) > 0.9). Clonal spread occurs only at short distances (< 1 m). Both clonal spread and limited dispersal, associated with sexual reproduction, contribute to the significant spatial genetic structure revealed by spatial autocorrelation analysis. The shape of the autocorrelogram suggests that seed dispersal is restricted and pollen flow extensive, which may be related to intense activity by insect pollinators. Clonal spread was more extensive in the lowly polluted zone than in the highly polluted zone. This cannot be interpreted as a strategy for promoting the propagation of adapted genotypes under the harshest ecological constraints (highest heavy metal concentrations). The higher fine-scale spatial genetic structure found in the lowly polluted zone can be ascribed to plant densities that were lower than in the highly polluted zone. No evidence of genetic divergence due to spatial heavy metal heterogeneity was found between lowly and highly polluted zones. 相似文献
906.
During retroviral particle formation, the capsid precursors (Gag) associate with the cell membrane via their matrix (MA) domain to form viral assembling particles. After budding, Gag and its proteolytically matured MA, form a shell in the released immature and mature particles, respectively. Although the arrangement of Gag domains in vitro and their radial organisation in retroviral particles have been extensively studied, little is known concerning Gag inter-subunit interactions in authentic retroviruses. We report that human T-cell leukemia virus type 1 Gag homodimerises in the cell via a disulphide bonding at cysteine 61 in the MA domain. Most Gags are homodimeric after budding and MAs are also dimeric in mature authentic virions. Molecular modelling of the MA domain indicates that non-covalent interactions at the MA dimer interface may also be important for Gag (and MA) dimerisation. In addition, all amino acids previously reported to be involved in MA-transmembrane (TM) interactions are located on the MA face opposite to the dimer interface. The model reveals that homodimerisation is compatible with a hexameric network of Gag and MA dimers that look like the hexameric networks observed for other retroviruses. These data, together with previous studies, lead us to propose a supra-molecular arrangement model in which the transmembrane glycoproteins of the virion envelope are anchored in a hexameric cage hole formed by the MA. 相似文献
907.
In the vertebrate embryo, spinal cord elongation requires FGF signaling that promotes the continuous development of the posterior nervous system by maintaining a stem zone of proliferating neural progenitors. Those escaping the caudal neural stem zone, which is expressed to Shh signal, initiate ventral patterning in the neural groove before starting neuronal differentiation in the neural tube. Here we investigated the integration of D-type cyclins, known to govern cell cycle progression under the control of extracellular signals, in the program of spinal cord maturation. In chicken embryo, we find that cyclin D2 is preferentially expressed in the posterior neural plate, whereas cyclin D1 appears in the neural groove. We demonstrated by loss- and gain-of-function experiments that FGF signaling maintains cyclin D2 in the immature caudal neural epithelium, while Shh activates cyclin D1 in the neural groove. Moreover, forced maintenance of cyclin D1 or D2 in the neural tube favors proliferation at the expense of neuronal differentiation. These results contribute to our understanding of how the cell cycle control can be linked to the patterning programs to influence the balance between proliferation and neuronal differentiation in discrete progenitors domains. 相似文献
908.
Structural differences have been reported in the glycosylation patterns of cystic fibrosis glycoproteins. Although the gene mutated in cystic fibrosis (CFTR) has been cloned and characterized as a chloride channel, its relationship to the highly viscous mucus and structural glycoprotein and mucin abnormalities in cystic fibrosis still remains to be defined. We have evaluated O-glycan biosynthesis in CHO and BHK cells that express CFTR and F508 CFTR as in vitro models, and utilized the cftr knockout mouse as an in vivo model of CFTR dysfunction. Activities of glycosyltransferases and sulfotransferases synthesizing mucin type O-glycan chains were determined in these models. Differences in transferase activity levels were found between tissues and cell types and during mouse development. No specific patterns of activities were associated with the lack of CFTR or with F508CFTR expression. This suggests that it is not the presence or absence of normal CFTR, or the presence of mutant CFTR alone, but rather cell specific additional factors or pathophysiological consequences that determine the changes in mucin glycosylation in cystic fibrosis. 相似文献
909.
The docking protein p130Cas has, together with FAK, been found as a target of the Yersinia virulence effector YopH. YopH is a protein tyrosine phosphatase that is delivered into host cells via the bacterial type III secretion machinery, and the outcome of its activity is inhibition of host cell phagocytosis. In the present study using p130Cas-/- cells, and p130Cas-/- cells expressing variants of GFPp130Cas, we show that this docking protein, via its substrate domain, is responsible for subcellular targeting of YopH in eukaryotic cells. Since YopH inhibits phagocytosis, p130Cas was expected to be critical for signalling mediating bacterial internalization. However, p130Cas-/- cells did not exhibit reduced capacity to internalize Yersinia. On the other hand, when a dominant negative variant of p130Cas was expressed in these cells, the phagocytic capacity was severely impaired. Moreover, the p130Cas-/- cells displayed a marked reduced sensitivity towards YopH-mediated detachment compared to wild-type cells. Transfecting these cells with full-length p130Cas rendered cells hypersensitive to both mechanical and Yersinia-mediated detachment. This hypersensitivity was not seen upon transfection with the dominant negative substrate domain-deleted variant of p130Cas. This implicates p130Cas as a prominent regulator of cell adhesion, where its substrate-binding domain has a significant function. 相似文献
910.
The reaper-binding protein scythe modulates apoptosis and proliferation during mammalian development 总被引:7,自引:0,他引:7
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Desmots F Russell HR Lee Y Boyd K McKinnon PJ 《Molecular and cellular biology》2005,25(23):10329-10337