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91.
92.
Metabotrophic glutamate receptors (mGluRs) modulate cellular activities involved in the processes of differentiation and degeneration.
In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5) in cerebral cortex,
corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I) as a function
of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was
studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic
rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90
weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem
the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression
was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem
and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly
in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M) stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression
in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration
in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in
calcium release has immense therapeutic application in insulin secretion and function. 相似文献
93.
Background
Cancer of the oral tongue is the second most common cancer among males in various parts of India. Despite advances in diagnosis and treatment the failure rates in cancer of the oral tongue are high and survival poor. Majority of these failures occur in untreated neck. 相似文献94.
Cordoba-Rodriguez R Fang H Lankford CS Frucht DM 《The Journal of biological chemistry》2004,279(20):20563-20566
Anthrax lethal toxin (LT), a critical virulence factor for Bacillus anthracis, has been demonstrated to cleave and to inactivate mitogen-activated protein kinase kinases (MAPKKs) that propagate prosurvival signals in macrophages (1-5). Whether this action of anthrax LT leads to the production of proinflammatory cytokines by macrophages has been more controversial (6, 7). We now report that anthrax LT treatment leads to the specific extracellular release of interleukin (IL)-1beta and IL-18 by the murine macrophage cell lines, RAW264.7 and J774A.1. Studies of the processing of IL-1beta reveal that the levels of activated/cleaved IL-1beta in RAW264.7 and J774.A1 cells are increased following treatment with anthrax LT. Enhanced processing of IL-1beta directly correlates with increased levels in the activation of its upstream regulator, IL-1beta-converting enzyme/Caspase-1 (ICE). The extracellular release of IL-1beta and IL-18 in response to anthrax LT is ICE-dependent, as an ICE-specific inhibitor blocks this process. These data indicate that ICE, IL-1beta, and IL-18 are downstream effectors of anthrax LT in macrophages, providing the basis for new bioassays for anthrax LT activity and representing potential therapeutic targets. 相似文献
95.
A study of the interaction of avidin with 2-anilinonaphthalene-6-sulfonic acid as a probe of the biotin binding site 总被引:3,自引:0,他引:3
The environment of the biotin binding site on avidin was investigated by determining the fluorescence enhancement of a series of fluorescent probes that are anilinonaphthalene sulfonic acid derivatives. Of the compounds tested, 2-anilinonaphthalene-6-sulfonic acid (2,6-ANS) exhibited the greatest enhancement under the conditions used (which would reflect both molar fluorescence enhancement and binding affinity) and exhibited more than 95% reversal upon addition of biotin. Thus, 2,6-ANS was chosen for more detailed characterization of the interaction with avidin. Only a single class of binding sites for 2,6-ANS was identified; the mean value for the Kd was 203 +/- 16 microM (X +/- 1 S.D.), and the molar ratio of 2,6-ANS binding sites to biotin binding sites was approx. 1. These results provide evidence that the biotin binding site and the 2,6-ANS binding site are at least partially overlapping, but the possibility that the probe binding site is altered by a conformational change induced by biotin binding cannot be excluded. At excitation = 328 nm and emission = 408 nm, the molar fluorescence of the bound probe was 6.8 +/- 1.0 microM-1 and that of the free probe was 0.061 +/- 0.008 microM-1 giving an enhancement ratio (molar fluorescence of bound probe/molar fluorescence of free probe) of 111 +/- 22. Upon binding, the wavelength of maximum fluorescence decreases. These findings also provide evidence that the fluorescence enhancement associated with the interaction of 2,6-ANS and avidin reflects the environment of the biotin binding site. The Kosower's Z factor, an empirical index of apolarity, was 82.1 for the 2,6-ANS binding site on avidin. This value reflects a degree of apolarity that is similar to apolar environments observed for substrate binding sites on several enzymes; although not the dominant factor, this environment may contribute to the strong binding of biotin. 相似文献
96.
97.
Tonic GABAergic inhibition of taste-responsive neurons in the nucleus of the solitary tract 总被引:4,自引:1,他引:3
The effects of gamma-aminobutyric acid (GABA) and the GABAA receptor
antagonist bicuculline methiodide (BICM) on the activity of taste-
responsive neurons in the nucleus of the solitary tract (NST) were examined
electrophysiologically in urethane-anesthetized hamsters. Single neurons in
the NST were recorded extracellularly and drugs (21 nl) were microinjected
into the vicinity of the cell via a multibarrel pipette. The response of
each cell was recorded to lingual stimulation with 0.032 M NaCl, 0.032 M
sucrose, 0.0032 M citric acid and 0.032 M quinine hydrochloride (QHCl).
Forty-six neurons were tested for the effects of GABA; the activity of 29
cells (63%) was inhibited by 5 mM GABA. Whether activity was elicited in
these cells by repetitive anodal current stimulation (25 microA, 0.5 s, 0.1
Hz) of the tongue (n = 13 cells) or the cells were spontaneously active (n
= 13 cells), GABA produced a dose-dependent (1, 2 and 5 mM) decrement in
activity. Forty- seven NST neurons were tested for the effects of BICM on
their responses to chemical stimulation of the tongue; the responses of 28
cells (60%) were enhanced by 10 mM BICM. The gustatory responses of 26 of
these cells were tested with three concentrations (0.2, 2 and 10 mM) of
BICM, which produced a dose-dependent increase in both spontaneous activity
and taste-evoked responses. Nine of these neurons were sucrose- best, seven
were NaCl-best, eight were acid-best and two responded best to QHCl. The
responses to all four tastants were enhanced, with no difference among
neuron types. For 18 cells that were tested with two or more gustatory
stimuli, BICM increased their breadth of responsiveness to their two most
effective stimuli. These data show that approximately 60% of the
taste-responsive neurons in the rostral NST are inhibited by GABA and/or
subject to a tonic inhibitory influence, which is mediated by GABAA
receptors. The modulation of these cells by GABA provides a mechanism by
which the breadth of tuning of the cell can be sharpened. Modulation of
gustatory activity following a number of physiological changes could be
mediated by such a GABAergic circuit.
相似文献
98.
Molecular evolution of the Sex-Ratio inversion complex in Drosophila pseudoobscura: analysis of the Esterase-5 gene region 总被引:2,自引:0,他引:2
The Sex-Ratio chromosome in Drosophila pseudoobscura is subject to meiotic
drive. It is associated with a series of three nonoverlapping paracentric
inversions on the right arm of the X chromosome. The esterase-5 gene region
has been localized to section 23 within the subbasal inversion of the
Sex-Ratio inversion complex, making esterase- 5 a convenient locus for
molecular evolutionary analyses of the Sex- Ratio inversion complex and the
associated drive system. A 504-bp fragment of noncoding, intergenic DNA
from the esterase-5 gene region was amplified and sequenced from 14
Sex-Ratio and 14 Standard X chromosomes of D. pseudoobscura, and from 9 X
chromosomes of its two sibling species, Drosophila persimilis and
Drosophila miranda. There is extensive sequence differentiation between the
Sex-Ratio and Standard chromosomal types. The common Standard chromosome is
highly polymorphic, while, as expected from either the neutral mutation
theory or the selective sweep hypothesis, the rarer Sex-Ratio chromosome
has much less within-chromosome nucleotide polymorphism. We estimate that
the Standard and Sex-Ratio chromosomes in D. pseudoobscura diverged between
700,000 and 1.3 Mya, or at least 2 million generations ago. The clustering
of D. pseudoobscura Sex-Ratio chromosomes in a neighbor- joining phylogeny
indicates a fairly old, monophyletic origin in this species. It appears
from these data that Sex-Ratio genes were present prior to the divergence
of D. pseudoobscura and D. persimilis and that both the Standard and
Sex-Ratio chromosomes of D. persimilis were derived from the Standard
chromosome of D. pseudoobscura after the inversion events that isolated the
D. pseudoobscura Sex-Ratio chromosome.
相似文献
99.
Nerve growth cone motility 总被引:1,自引:0,他引:1
Although many issues remain unresolved, the past year has witnessed a number of advances in our understanding of the inter-relationships between extracellular influences, cell phenotype, growth associated proteins, second messengers, and cytoskeletal components in the control of neurite outgrowth and growth cone behavior. Some of the early events associated with process initiation have been tentatively identified, and more is known about the assembly and stabilization of the microtubular framework of growing neurites. The mechanical forces involved in neurite extension have begun to be quantified, and interactions between the actin and microtubule systems are being further characterized. The current data more strongly support a functional role for GAP-43 in control of motility. The data also tend to support a central role for cytoplasmic calcium in mediating the actions of many growth-regulating influences, and strongly implicate changes in actin filament stability as mediating the behavioral effects of calcium. 相似文献
100.
Although it is now apparent that the intracellular pH may rise considerably above neutrality under physiological conditions, information on the effect of alkaline pH on microtubule assembly and disassembly is still quite fragmentay. We have studied the assembly/disassembly of bovine brain microtubule protein at alkaline pH in vitro. When microtubules are assembled to a new steady state at pH less than 7 and pH is then made more alkaline, they undergo a rapid disassembly to a new steady state. This disassembly is reversed by acidification. The degree of disassembly is determined largely by the pH- dependence of the critical concentration, which increases five to eight times, from pH 7 to 8. A fraction of assembly-incompetent tubulin is identified that increases with pH, but its incompetency is largely reversed with acidification. Measurements of microtubule lengths are used to indicate that disassembly occurs by uniform shortening of microtubules. A comparison of shortening by alkalinization with dilution suggests that the intrinsic rate of disassembly is accelerated by increasing pH. The capacity for initiating assembly is progressively lost with incubation at alkaline pH (although some protection is afforded by sulfhydryl-reducing agents). However, direct assembly from depolymerized mixtures is possible at least up to pH 8.3, and the steady state achieved at these alkaline pH values is stable. Such preparations are readily disassembled by cold and podophyllotoxin (PLN). Disassembly induced by PLN is also markedly enhanced at alkaline pH, suggesting a corresponding enhancement of “treadmilling.” The implications of physiological events leading to alkaline shifts of pH for microtubule assembly/disassembly are discussed, particularly in the light of recent hypotheses regarding treadmilling and its role in controlling the distribution of microtubules in vivo. 相似文献