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41.
P. Schubert T. Ogata S. Ferroni A. McRae Y. Nakamura K. Rudolphi 《Journal of molecular neuroscience : MN》1996,28(1-3):185-190
In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative
diseases, we investigated the underlying molecular signaling as a possible target for a pharmacological therapy. Here, we
are particularly focusing on the endogenous modulation of the Ca2+ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the xanthine derivative propentofylline
(PPF). As an experimental model, we used cultured rat microglial cells and astrocytes that are immature, show a high proliferation
rate, and resemble in several aspects pathologically activated glial cells. A prolonged increase of the cellular cAMP level
favored the differentiation of cultured astrocytes and associated properties required for the physiological nerve cell function.
On the other hand, a strengthening of the cyclic nucleotide-dependent signaling inhibited potentially neurotoxic properties
of cultured microglial cells. Similar effects were obtained by treatment with propentofylline, which mimicked modulatory adenosine
effects and increased the intracellular level of cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by
modifying the strength and the timing of these second messengers, may provide a therapy of neurodegenerative diseases in which
a pathological activation of microglial cells and astrocytes is discussed to play a pathogenic role. 相似文献
42.
Klaus-Dietmar Merboldt Gunnar Krüger Wolfgang Hnicke Andreas Kleinschmidt Jens Frahm 《Magnetic resonance in medicine》1995,34(4):639-644
Functional mapping of human brain activation has been accomplished at high spatial and temporal resolution (voxel size 4.9 μl, temporal increment 100 ms). The approach was based on oxygenation-sensitive long-echo time FLASH MRI sequences synchronized to multiply repeated cycles of visual stimulation in a CINE acquisition mode. This high temporal resolution revealed that stimulus-related signal intensity changes in human visual cortex display an initial latency followed by increases extending over several seconds. Furthermore, the temporal characteristics of the complete CINE MRI signal time course depended on the absolute and relative durations of activation and control periods and, for example, caused an apparent absence of a poststimulation “undershoot” phenomenon. Complementing hyperoxygenation due to rapid hemodynamic adjustments, these results suggest signal intensity modulation by enhanced oxygen consumption and concomitant deoxygenation during prolonged and/or repetitive stimulation. 相似文献
43.
J. Blasi G. Egea M. J. Castiella M. Arribas C. Solsona P. J. Richardson J. Marsal 《Journal of neural transmission (Vienna, Austria : 1996)》1992,90(2):87-102
Summary Torpedo electric organ has been used to study the binding of botulinum neurotoxin type A to pure cholinergic synaptosomes and presynaptic plasma membrane.125I-labeled botulinum neurotoxin type A exhibits specific binding to cholinergic fractions. Two binding sites have been determined according to data analysis: a high affinity binding site (synaptosomes: Kd=0.11±0.03 nM, Bmax=50±10 fmol · mg prot–1; presynaptic plasma membrane: Kd=0.2±0.05 nM, Bmax=150±15 fmol · mg prot–1) and a low affinity binding site (synaptosomes: Kd 26 nM, Bmax 7.5 pmol · mg prot–1; presynaptic plasma membrane: Kd 30 nM, Bmax 52 pmol · mg prot–1). The binding of125I-botulinum neurotoxin type A is decreased by previous treatment of synaptosomes by neuraminidase and trypsin, and by a preincubation with bovine brain gangliosides or antiserum raised against Torpedo presynaptic plasma membrane. When presynaptic plasma membranes are blotted to nitrocellulose sheet, either125I-botulinum neurotoxin or botulinum toxin-gold complexes bind to a Mr 140,000 protein. Botulinum toxin-gold complexes have also been used to study the toxin internalization process into Torpedo synaptosomes. The images fit the three step sequence model in the pathway of botulinum neurotoxin poisoning. 相似文献
44.
It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal enterotoxin A (SEA), could up-regulate B7-2 on most splenic APC independently of the CD154-CD40 interaction, followed by efficient expansion of SEA-reactive V(beta)3(+) T cells in CD154- or CD40-deficient mice. However, the CD154-CD40 interaction may be involved in SEA-mediated T cell activation, since a contribution of the CD154-CD40 interaction was observed when a lower dose of SEA was injected. CD154-independent T cell priming by SEA appeared also independent of the TRANCE-RANK pathway, which was shown to be capable of mediating CD154-independent activation of naive T cells during the infection of some viruses. These results indicate that SEA, which provokes rapid and efficient T cell responses without adjuvant, could utilize multiple CD154/TRANCE-independent pathways, to prime T cells. 相似文献
45.
46.
Ca2+-and voltage activated K+ channel in apical cell membrane of gallbladder epithelium fromTriturus
Y. Maruyama H. Matsunaga T. Hoshi 《Pflügers Archiv : European journal of physiology》1986,406(6):563-567
The presence of Ca2+- and voltage-activated K+ channels was directly demonstrated in the apical cell membrane of gallbladder epithelium by patch-clamp single-channel current recording. In K+-depolarized epithelial cells, negative pipette potentials induced outward current steps when the patch-pipette was filled with Na+-rich solution and these current steps were not affected by the presence or absence of Cl–. When K+-rich solution was in the pipette and K+-depolarized cells were examined, the current-voltage relations were linear with a single-channel conductance of 140 pS and polarity was reversed at 0 mV. In excised inside-out membrane patches, raising the free Ca2+ concentration of the medium facing the inner side of the membrane from 10–7 to 10–6 M evoked a marked increase in open state probability of the channels without affecting the elementary current steps. This suggests that intracellular Ca2+ as a second messenger plays a crucial role in the regulatory mechanism of the membrane potential by modulating the high-conductance apical K+ channels. 相似文献
47.
Bonnie B. Punske Wayne E. Cascio Connie Engle H. Troy Nagle Leonard S. Gettes Timothy A. Johnson 《Annals of biomedical engineering》1998,26(6):1010-1021
This study applied zero-delay wave number spectral estimation as a means of quantifying the changes in activation and recovery sequences of propagating plane waves on the epicardial surface of in situ porcine hearts during regional hyperkalemia and ischemia. Unipolar electrograms (104) were recorded from the left ventricular surface of nine hearts using a plaque electrode array with 1 mm spatial sampling intervals. The objectives were (1) to define a set of parameters capable of quantifying the spatial and temporal changes in measured extracellular potentials associated with localized ischemia prior to the onset of conduction block; (2) to elevate regional levels of extracellular potassium ion concentration and quantify potential changes due to this known physiologic manipulation; and (3) to use quantitative parameters to make statistical comparisons in order to distinguish wave fronts during normal, ischemic and hyperkalemic conditions. Results showed that the parameters of wave number and average temporal frequency and the associated power, as determined from the wave number spectrum, provided statistically significant (p < 0.05) quantification of changes in wave front features during normal and ischemic or hyperkalemic conditions. The results were consistent with results obtained from conventional time–space domain methods like isochronal mapping and electrograms, with the advantage of a quantitative result enabling simple comparisons and trend analysis for large numbers of heart beats. © 1998 Biomedical Engineering Society.
PAC98: 8759Wc, 8722Fy, 8780+s 相似文献
48.
CD5 is expressed on thymocytes, all mature T cells, and a subset of mature B cells, and probably contributes to T-cell–B-cell adhesion. We assessed whether CD5-crosslinking by mAb augments T-cell stimulation. Plate-bound anti-CD5 or anti-CD3 mAb alone had no effect on any of the assessed activation parameters of resting T cells. However, concomitant signaling through both CD5 and CD3 by plate-bound antibodies resulted in marked increases in T-cell surface CD69 expression and T-cell metabolism, as assessed by the T cell's ability to reduce 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) to formazen. In addition, simultaneous cross-linking of CD5 and CD3 caused a significant (p < 0.001) increase in phosphatidylinositol hydrolysis in resting T cells compared to stimulation with anti-CD3 mAb alone or anti-CD3 mAb plus anti-CD5 isotype control antibody. These results indicate that CD5 augments signaling through CD3 and consequently functions as a costimulatory molecule for resting T cells. 相似文献
49.
To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [14C]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalocortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease. 相似文献
50.
Guanine nucleotide exchange factors of the cytohesin family and their roles in signal transduction 总被引:2,自引:0,他引:2
Waldemar Kolanus 《Immunological reviews》2007,218(1):102-113
Summary: Members of the cytohesin protein family, a group of guanine nucleotide exchange factors for adenosine diphosphate ribosylation factor (ARF) guanosine triphosphatases, have recently emerged as important regulators of signal transduction in vertebrate and invertebrate biology. These proteins share a modular domain structure, comprising carboxy-terminal membrane recruitment elements, a Sec7 homology effector domain, and an amino-terminal coiled-coil domain that serve as a platform for their integration into larger signaling complexes. Although these proteins have a highly similar overall build, their individual biological functions appear to be at least partly specific. Cytohesin-1 had been identified as a regulator of β2 integrin inside-out regulation in immune cells and was subsequently shown to be involved in mitogen-associated protein kinase signaling in tumor cell proliferation as well as in T-helper cell activation and differentiation. Cytohesin-3, which had been discovered to be strongly associated with T-cell anergy, was very recently described as an essential component of insulin signal transduction in Drosophila and in human and murine liver cells. Future work will aim to dissect the mechanistic details of the modes of action of the cytohesins as well as to define the precise roles of these versatile proteins in vertebrates at the genetic level. 相似文献