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991.
We previously reported that αA-crystallin and protease-activated receptor are involved in protection of astrocytes against C2-ceramide- and staurosporine-induced cell death (Li et al., 2009). Here, we investigated the molecular mechanism of αA-crystallin-mediated cytoprotection. We found that the expression of mutants mimicking specific phosphorylation of αA-crystallin increases the protection of astrocytes. However, the expression of mutants mimicking unphosphorylation of αA-crystallin results in loss of protection. These data revealed that the phosphorylation of αA-crystallin at Ser122 and Ser148 is required for protection. Furthermore, we explored the mechanism of cytoprotection of astrocytes by αA-crystallin. Application of specific inhibitors of p38 and ERK abrogates the protection of astrocytes by over-expression of αA-crystallin. Thus, p38 and ERK contribute to protective processes by αA-crystallin. This is comparable to our previous results which demonstrated that p38 and ERK regulated protease-activated receptor-2 (PAR-2)/αB-crystallin-mediated cytoprotection. Furthermore, we found that PAR-2 activation increases the expression of αA-crystallin. Thus, endogenous αA-crystallin protects astrocytes via mechanisms, which regulate the expression and/or phosphorylation status of αA-crystallin. 相似文献
992.
Schwandt T Schumak B Gielen GH Jüngerkes F Schmidbauer P Klocke K Staratschek-Jox A van Rooijen N Kraal G Ludwig-Portugall I Franken L Wehner S Kalff JC Weber O Kirschning C Coch C Kalinke U Wenzel J Kurts C Zawatzky R Holzmann B Layland L Schultze JL Burgdorf S den Haan JM Knolle PA Limmer A 《The EMBO journal》2012,31(1):201-213
Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis. 相似文献
993.
Shi-Xiong Tan Yvonne Ng James G. Burchfield Georg Ramm David G. Lambright Jacqueline St?ckli David E. James 《Molecular and cellular biology》2012,32(24):4946-4959
The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila. This region also contains a nonoverlapping intracellular GLUT4-containing storage vesicle (GSV) cargo-binding site. The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation. Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity. We propose a model wherein AS160 acts as a regulatory switch in the docking and/or fusion of GSVs with the PM. 相似文献
994.
Studies in anesthetized animals have suggested that activity in early visual cortex is mainly driven by visual input and is well described by a feedforward processing hierarchy. However, evidence from experiments on awake animals has shown that both eye movements and behavioral state can strongly modulate responses of neurons in visual cortex; the functional significance of this modulation, however, remains elusive. Using visual-flow feedback manipulations during locomotion in a virtual reality environment, we found that responses in layer 2/3 of mouse primary visual cortex are strongly driven by locomotion and by mismatch between actual and expected visual feedback. These data suggest that processing in visual cortex may be based on predictive coding strategies that use motor-related and visual input to detect mismatches between predicted and actual visual feedback. 相似文献
995.
Pyruvate and 2-oxoglutarate dehydrogenase complexes are strongly inhibited by phytanoyl-CoA (IC(50) approximately 10(-6)-10(-7) M). Palmitoyl-CoA is 10-fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3 mM. At the substrate saturation, the acyl-CoA's affect the first and second enzymatic components of the 2-oxoglutarate dehydrogenase complex, while the third component is inhibited only at a low saturation with its substrate dihydrolipoamide. Thus, key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid. Decreased activity of the complexes might therefore contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease. 相似文献
996.
Radon K Spegel H Meyer N Klein J Brix J Wiedenhofer A Eder H Praml G Schulze A Ehrenstein V von Kries R Nowak D 《Bioelectromagnetics》2006,27(1):77-81
The aim of our study was to test the feasibility and reliability of personal dosimetry. Twenty-four hour exposure assessment was carried out in 42 children, 57 adolescents, and 64 adults using the Maschek dosimeter prototype. Self-reported exposure to mobile phone frequencies were compared with the dosimetry results. In addition, dosimetry readings of the Maschek device and those of the Antennessa DSP-090 were compared in 40 subjects. Self-reported exposures were not associated with dosimetry readings. The measurement results of the two dosimeters were in moderate agreement (r(Spearman) = 0.35; P = .03). Personal dosimetry for exposure to mobile phone base station might be feasible in epidemiologic studies. However, the consistency seems to be moderate. 相似文献
997.
998.
The mixed-metal trinuclear cluster cations [H3Ru2(C6Me6)2Os(C6H6)(O)]+ (1), [H3Ru2(1,2,4,5-C6H2Me4)2Os(p-MeC6H4iPr)(O)]+ (2) and [H3Ru2(1,2,4,5-C6H2Me4)2Os(C6H6)(O)]+ (3) have been synthesised from the corresponding dinuclear precursors [H3Ru2(arene)2]+ and the corresponding mononuclear complexes [Os(arene)(H2O)3]2+, isolated and characterised as the tetrafluoroborate and hexafluorophosphate salts. The cations 1, 2 and 3 are heteronuclear analogues of the cluster cation [H3Ru3(C6H6)(C6Me6)2(O)]+ that possesses a homonuclear metallic core. The single-crystal X-ray structure analyses of [1][BF4], [2][PF6] and [3][PF6] reveal an equiangular metal triangle despite the presence of an osmium atom in the metallic core. 相似文献
999.
The dinuclear arene ruthenium complexes [RuCl2{C6H5(CH2)3OCO-p-C6H4-OC8H17}]2 (1) and [RuCl2{p-C6H4(CH2COOCH2CH3)2}]2 (2) have been obtained by dehydrogenation of the corresponding cyclohexadiene derivative with ruthenium chloride hydrate. The single-crystal X-ray structure analysis of 2 shows the arene ligands to be involved in slipped-parallel π-π stacking interactions with neighbouring molecules, thus forming infinite chains along the b-axis. The dinuclear complexes 1 and 2 react with two equivalents of triphenylphosphine (PPh3) to give in excellent yield the corresponding mononuclear phosphine complexes [RuCl2{C6H5(CH2)3OCO-p-C6H4-OC8H17}(PPh3)] (3) and [RuCl2{p-C6H4(CH2COOCH2CH3)2}(PPh3)] (4), respectively. The single-crystal X-ray structure analysis of 4 reveals the formation of a dimer through two C-H?Cl interactions in the solid state. 相似文献
1000.