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991.
Activin, a member of the transforming growth factor-beta superfamily, is an endocrine hormone that regulates differentiation and proliferation of a wide variety of cells. In the brain, activin protects neurons from ischemic damage. In this study, we demonstrate that activin modulates anxiety-related behavior by analyzing ACM4 and FSM transgenic mice in which activin and follistatin (which antagonizes the activin signal), respectively, were overexpressed in a forebrain-specific manner under the control of the alphaCaMKII promoter. Behavioral analyses revealed that FSM mice exhibited enhanced anxiety compared to wild-type littermates, while ACM4 mice showed reduced anxiety. Importantly, survival of newly formed neurons in the subgranular zone of adult hippocampus was significantly decreased in FSM mice, which was partially rescued in ACM4/FSM double transgenic mice. Our findings demonstrate that the level of activin in the adult brain bi-directionally influences anxiety-related behavior. These results further suggest that decreases in postnatal neurogenesis caused by activin inhibition affect an anxiety-related behavior in adulthood. Activin and its signaling pathway may represent novel therapeutic targets for anxiety disorder as well as ischemic brain injury. 相似文献
992.
Cui Y Mirkia K Florence Fu YH Zhu L Yokoyama KK Chiu R 《Journal of cellular biochemistry》2002,86(4):630-641
The retinoblastoma susceptibility gene product, p105Rb (RB), is generally believed to be an important regulator in the control of cell growth, differentiation, and apoptosis. Several cellular factors that form complexes with RB and exert their cellular regulatory functions have been identified, such as the newly identified RB:cyclophilin A (CypA) complex. The physical interactions between RB and CypA were demonstrated by glutathione S-transferase affinity matrix binding assays and immunoprecipitation, followed by Western blot analyses. The N-terminal region of CypA mediated the interaction with RB, whereas the region upstream of the A-pocket of RB was required for binding to CypA. Ectopic expression of RB into Jurkat cells partially blocks the function of cyclosporin (CsA) to inhibit nuclear factor for activation of T cell (NFAT) activation by phorbol ester (PMA) plus ionomycin A (IA), suggesting that RB may prevent CsA inhibition of T lymphocyte activation. These results are further evidenced by the effect of RB on both calcineurin (CN) and NFAT binding activity in vitro, suggesting that the interaction of RB with CypA interferes with the CsA:CypA complex and blocks CsA-inhibited CN activity. These data reveal the functional link between RB and CypA and their involvement in T cell activation signaling. 相似文献
993.
Mechanism of resistance to benzalkonium chloride by Pseudomonas aeruginosa. 总被引:4,自引:0,他引:4
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The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than those in the cell walls of susceptible P. aeruginosa. The amounts of BC adsorbed to PL and FNL of cell walls of BC-resistant P. aeruginosa were lower than those for BC-susceptible P. aeruginosa. Fifteen species of cellular fatty acids were identified by capillary gas chromatography and gas chromatography-mass spectrometry. The ability of BC to permeate the cell wall was reduced because of the increase in cellular fatty acids. These results suggested that the resistance of P. aeruginosa to BC is mainly a result of increased in the contents of PL and FNL. In resistant P. aeruginosa, the decrease in the amount of BC adsorbed is likely to be the result of increases in the contents of PL and FNL. 相似文献
994.
Kuwasako K Takahashi M Tochio N Abe C Tsuda K Inoue M Terada T Shirouzu M Kobayashi N Kigawa T Taguchi S Tanaka A Hayashizaki Y Güntert P Muto Y Yokoyama S 《Biochemistry》2008,47(24):6437-6450
T cell intracellular antigen-1 (TIA-1), an apoptosis promoting factor, functions as a splicing regulator for the Fas pre-mRNA. TIA-1 possesses three RNA recognition motifs (RRMs) and a glutamine-rich domain. The second RRM (RRM2) is necessary and sufficient for tight, sequence-specific binding to the uridine-rich sequences buried around the 5' splice sites. In the present study, we solved the solution structure of the murine TIA-1 RRM2 by heteronuclear-nuclear magnetic resonance spectroscopy. The TIA-1 RRM2 adopts the RRM fold (betaalphabetabetaalphabeta) and possesses an extra beta-strand between beta2 and beta3, which forms an additional beta-sheet with the C-terminal part of beta2. We refer to this structure as the beta2-beta2' beta-loop. Interestingly, this characteristic beta-loop structure is conserved among a number of RRMs, including the U2AF65 RRM2 and the Sex-lethal RRM1 and RRM2, which also bind to uridine-rich RNAs. Furthermore, we identified a new sequence motif in the beta2-beta2' beta-loop, the DxxT motif. Chemical shift perturbation analyses of both the main and side chains upon binding to the uridine pentamer RNA revealed that most of the beta-sheet surface, including the beta2-beta2' beta-loop, is involved in the RNA binding. An investigation of the chemical shift perturbation revealed similarity in the RNA recognition modes between the TIA-1 and U2AF65 RRMs. 相似文献
995.
The effect of inhibition of acylCoA: cholesterol acyltransferase (ACAT) was studied on high density lipoprotein (HDL) metabolism. An inhibitor of ACAT, MCC-147, was given mouse peritoneal macrophages and expression of ATP-binding cassette transporter A1 (ABCA1) was examined. ABCA1 was increased both at the mRNA and protein levels, only when the cells are cholesterol-loaded and thereby the inhibitor decreased esterified cholesterol and increased unesterified cholesterol. In this condition, the ACAT inhibitor increased reversible binding of apoA-I to the cells and enhanced apoA-I-mediated release of cellular cholesterol and phospholipid, but did not influence nonspecific cellular cholesterol efflux to lipid microemulsion. It was therefore concluded that the ACAT inhibitor increased the release of cholesterol from the cholesterol-loaded macrophages by increasing the expression of ABCA1, putatively through shifting cholesterol distribution from the esterified to the free compartments. 相似文献
996.
997.
Date M Yokoyama K Umezawa Y Matsui H Kikuchi Y 《Applied and environmental microbiology》2003,69(5):3011-3014
We previously observed secretion of active-form transglutaminase in Corynebacterium glutamicum by coexpressing the subtilisin-like protease SAM-P45 from Streptomyces albogriseolus to process the prodomain. However, the N-terminal amino acid sequence of the transglutaminase differed from that of the native Streptoverticillium mobaraense enzyme. In the present work we have used site-directed mutagenesis to generate an optimal SAM-P45 cleavage site in the C-terminal region of the prodomain. As a result, native-type transglutaminase was secreted. 相似文献
998.
Duo Jin Shin-ichi Muramatsu Nobuaki Shimizu Shigeru Yokoyama Hirokazu Hirai Kiyofumi Yamada Hong-Xiang Liu Chiharu Higashida Minako Hashii Akihiko Higashida Masahide Asano Shoji Ohkuma Haruhiro Higashida 《Neurochemistry international》2012
A 16-kDa proteolipid, mediatophore, in Torpedo electric organs mediates Ca2+-dependent acetylcholine release. Mediatophore is identical to the pore-forming stalk c-subunit of the V0 sector of vacuolar proton ATPase (ATP6V0C). The function of ATP6V0C in the mammalian central nervous system is not clear. Here, we report transfection of adeno-associated viral vectors harboring rat ATP6V0C into the mouse substantia nigra, in which high potassium stimulation increased overflow of endogenous dopamine (DA) measured in the striatum by in vivo microdialysis. Next, in the striatum of 6-hydroxydopamine-lesioned mice, a model of Parkinson’s disease (PD), human tyrosine hydroxylase, aromatic l-amino-acid decarboxylase and guanosine triphosphate cyclohydrolase 1, together with or without ATP6V0C, were expressed in the caudoputamen for rescue. Motor performance on the accelerating rotarod test and amphetamine-induced ipsilateral rotation were improved in the rescued mice coexpressing ATP6V0C. [3H]DA, taken up into cultured N18 neuronal tumor cells transformed to express ATP6V0C, was released by potassium stimulation. These results indicated that ATP6V0C mediates DA release from nerve terminals in the striatum of DA neurons of normal mice and from gene-transferred striatal cells of parkinsonian mice. The results suggested that ATP6V0C may be useful as a rescue molecule in addition to DA-synthetic enzymes in the gene therapy of PD. 相似文献
999.
Cyclic ADP-ribose (cADPR), a known endogenous modulator of ryanodine receptor Ca2+ releasing channels, is found in the nervous system. Injection of cADPR into neuronal cells primarily induces a transient elevation of intracellular Ca2+ concentration ([Ca2+]i), and/or secondarily potentiates [Ca2+]i increases that are the result of depolarization-induced Ca2+ influx. Acetylcholine release from cholinergic neurons is facilitated by cADPR. cADPR modifies K+ currents or elicits Ca2+-dependent inward currents. cADPR is synthesized by both membrane-bound and cytosolic forms of ADP-ribosyl cyclase in neuronal cells. cADPR hydrolase activity is weak in the membrane fraction, but high in the cytoplasm. Cytosolic ADP-ribosyl cyclase activity is upregulated by nitric oxide/cyclic GMP-dependent phosphorylation. Stimulation of muscarinic and beta-adrenergic receptors activates membrane-bound ADP-ribosyl cyclase via G proteins within membranes of neuronal tumor cells and cortical astrocytes. These findings strongly suggest that cADPR is a second messenger in Ca2+ signaling in the nervous system, although many intriguing issues remain to be addressed before this identity is confirmed. 相似文献
1000.
The aim of this work was to examine the applicability of the anaerobic ammonium oxidation (anammox) process to three kinds of low BOD/N ratio wastewaters from animal waste treatment processes in batch mode. A rapid decrease of NO(2)(-) and NH(4)(+) was observed during incubation with wastewaters from AS and UASB/trickling filter and their corresponding control artificial wastewaters. This nitrogen removal resulted from the anammox reaction, because the ratio of removed NO(2)(-) and NH(4)(+) was close to the theoretical ratio of the anammox reaction. Comparison of the inorganic nitrogen removal rate of the actual wastewater and that of control artificial wastewater showed that these two kinds of wastewater were very suitable for anammox treatment. Incubation with wastewater from RW did not show a clear anammox reaction; however, diluting it by half enabled the reaction, suggesting the presence of an inhibitory factor. This study showed that the three kinds of wastewater from animal waste treatment processes were suitable for anammox treatment. 相似文献