Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Why is it that oligodendrocytes do not normally express major histocompatibility complex (MHC) molecules? To examine the effect of aberrant MHC expression in oligodendrocytes, transgenic mice have been produced which expressed the class I MHC gene, H-2Kb, under direction of the MBP promoter [Turnley et al. (1991b) Nature, 353:566-569; Yoshioka et al. (1991) Mol. Cell. Biol., 11:5479-5486]. A proportion of these mice exhibited a shivering phenotype, with tonic seizures and early death. Oligodendrocyte function and viability was shown to be affected, resulting in severe dysmyelination of the CNS. Is this phenomenon of cell damage due to aberrant expression of MHC molecules restricted to oligodendrocytes, and could other, non-MHC molecules, when aberrantly expressed, result in similar cell damage? This paper discusses these questions and examines possible mechanisms for the oligodendrocyte damage and hypomyelination observed in these transgenic mice. Finally, the implications of aberrant MHC expression in oligodendrocytes for demyelinating diseases such as multiple sclerosis are discussed.
 ...
PMID:Dysmyelination in class I MHC transgenic mice. 857 78

We evaluated whether tolerance to the antagonism of bicuculine-induced seizures by diazepam is associated with changes (i) in the content of mRNAs encoding for gamma-aminobutyric acidA (GABAA) receptor subunits, (ii) in the expression density of these subunits, and (iii) in the 1,4-benzodiazepine binding site characteristics in discrete neocortical structures. We found that in diazepam-tolerant rats, the content of the mRNA encoding for the alpha 1 subunit of the GABAA receptor decreased in the frontoparietal motor (FrPaM) cortex and in the hippocampus (42% and 20%, respectively) but not in the frontoparietal somatosensory (FrPaSS) cortex, striatum, olfactory bulb, and cerebellum. In the FrPaM cortex, gamma 2S and gamma 2L subunit mRNA contents were also decreased (48% and 30%, respectively), whereas that of alpha 5 was increased (30%). In the FrPaM and FrPaSS cortices as well as in cerebellum of diazepam-tolerant rats, the content of alpha 2, alpha 3, alpha 6, beta 2, and delta subunit mRNA was unchanged, as was the content of alpha 2, alpha 5, gamma 1, and gamma 2S subunit mRNA in the hippocampus. Furthermore, the reduction in alpha 1 subunit mRNA content in the FrPaM cortex and the anticonvulsant tolerance to diazepam returned to control values 72 hr after termination of the protracted diazepam treatment. Rats receiving a treatment with imidazenil in doses equipotent and with a schedule identical to that of diazepam failed to exhibit tolerance to the anticonvulsant action of this drug or cross-tolerance to diazepam. In these rats, the content of mRNA encoding for alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, gamma 1, gamma 2S, gamma 2L, and delta GABAA receptor subunits failed to change in the FrPaM and FrPaSS cortices, in the hippocampus, and in the other brain areas that were studied in diazepam-tolerant rats. Although the density and affinity of [3H]flumazenil and [3H]imidazenil binding failed to change in the FrPaM and FrPaSS cortices of diazepam-tolerant rats, the expression density of alpha 1 subunit immunogold labeling decreased by 37%, whereas that of alpha 5, gamma 2L/S, and beta 2/3 increased by 158%, 50%, and 47%, respectively, in the FrPaM cortex, and the density of the alpha 5 subunit selectively increased (209%) in the FrPaSS cortex. In contrast, the immunogold labeling density of the alpha 1, alpha 5, gamma 2L/S, and beta 2/3 subunits failed to change in either the FrPaM or FrPaSS cortex of rats receiving protracted imidazenil treatment.
Mol Pharmacol 1996 May
PMID:Modifications of gamma-aminobutyric acidA receptor subunit expression in rat neocortex during tolerance to diazepam. 862 32

A new method for comparing protein structures, based on a minimal surface metric, is developed. A virtual polypeptide backbone is created by joining consecutive C alpha atoms in a protein structure. The minimal surface between the virtual backbones of two proteins (the Area Functional) is determined numerically using an iterative triangulation strategy. The first protein is then rotated and translated in space until the smallest minimal surface is obtained. Such a technique yields the optimal structural superposition between two protein segments. It requires no initial sequence alignment, is relatively insensitive to insertions and deletions, and obviates the need to select a gap penalty. The optimal minimal area can then be converted to the Area-C alpha distance, measured in angstroms, to determine the structural similarity. This technique has been applied to a large class of proteins and is able to detect not only small-scale differences between closely related proteins but also large-scale topological similarities between evolutionary unrelated proteins that lack any obvious sequence homology. To measure the similarity between structurally dissimilar proteins, an additional measure (the Fit Comparison) is developed. This is a scale-invariant measure of a structural similarity that is useful for determining topological similarities between dissimilar proteins with unrelated sequences.
J Mol Biol 1996 May 24
PMID:A surface of minimum area metric for the structural comparison of proteins. 863 17

alpha-Guanidinoglutaric acid (alpha-GGA) was first isolated from the cobalt-induced epileptic focus of cat cerebral cortex by us in 1980. alpha-GGA could induce behavioral convulsion as well as electroencephalography-documented epileptic seizures, when it was administered into the brain. alpha-GGA was also found to be a potent nitric oxide synthase inhibitor, suggesting that suppression of this activity may result in epileptic seizures. It is now observed that alpha-GGA generates reactive oxygen species as superoxide and hydroxyl radicals in aqueous solution. These findings suggest that reactive oxygen species may damage cell membranes, thus leading to neuronal depolarization, which is closely related to epileptogenesity.
Biochem Mol Biol Int 1995 Oct
PMID:alpha-Guanidinoglutaric acid as a free radical generator. 867 21

Cholecystokinin (CCK) can be a potent anticonvulsant neuropeptide in certain seizure models. Therefore, we examined whether seizures produced by electrical kindling of the amygdala or electroconvulsive seizures (ECS) would affect the expression of CCK mRNA in rat brain. Following a single kindled seizure, CCK mRNA expression was decreased about 20-58% in the amygdala. In contrast, after multiple consecutive kindled seizures, CCK mRNA expression was increased in the amygdala, cerebral cortex, CA1 pyramidal cell layer of the hippocampus and dentate hilus. A single ECS produced no effect on CCK mRNA expression, but multiple ECS increased expression in the interneurons of the hippocampus 24 h after the last seizure. Since seizures produced by ECS can be anticonvulsant to further ECS or kindled seizures, the CCK increases in the hippocampus may represent a compensatory anticonvulsant adaptation observed in both models. Overall, the kindling-induced alterations in CCK expression appear to be more complex involving multiple brain regions and distinct temporal properties.
Brain Res Mol Brain Res 1996 Jan
PMID:Changes in cholecystokinin mRNA expression after amygdala kindled seizures: an in situ hybridization study. 871 64

The neural basis underlying the cognitive side effects of ECT is unknown. Recent studies suggest that the memory dysfunction may be caused by alterations in hippocampal synaptic efficacy [20]. In situ hybridisation was used to examine the possible receptor mechanisms responsible for this effect. Repeated ECS markedly increased mRNA expression for the GluR1 subunit of the AMPA receptor, but not the NMDAR1A-G subtypes of the NMDA receptor, relative to control treatments. This effect was present 24 h after the last seizure and may be responsible for the expression of the ECS-induced increase in synaptic efficacy.
Brain Res Mol Brain Res 1996 Jan
PMID:Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus. 871 76

Nuclear hormone receptors are thought to play important roles in the regulation of gene expression in the hippocampus. We report here the isolation of an additional member of this superfamily, HZF-3, which is expressed preferentially in the rat brain and therein within the hippocampus. HZF-3 cDNA encodes a 66.6-kDa protein with high homology to the inducible nuclear orphan receptors NURR1/NOT and NGFI-B. Like NURR1/NOT and NGFI-B, HZF-3 mRNA accumulates in PC12 cells subsequent to membrane depolarization. In the rat brain, HZF-3 expression is induced following seizures elicited by the chlorinated insecticide lindane. The time course of HZF-3 induction by membrane depolarization in PC12 cells and seizures in animals is more prolonged than that observed for other immediate-early genes, such as NGFI-B. Electrophoretic mobility shift assays demonstrated HZF-3 to interact specifically with the same DNA target element as NGFI-B: NBRE. These results suggest HZF-3 is a member of a distinct family of inducible orphan receptors which are likely to display synergistic and/or antagonistic regulatory functions in mediating signal-induced transcriptional responses in the nervous system.
Brain Res Mol Brain Res 1996 May
PMID:HZF-3, an immediate-early orphan receptor homologous to NURR1/NOT: induction upon membrane depolarization and seizures. 873 62

In situ hybridization histochemistry was used to evaluate the expression of the immediate-early gene c-fos following the induction of audiogenic seizures in adult rats with transient neonatal hypothyroidism. The rats treated with 0.02% propylthiouracil (PTU) through mother's milk during days 0-19 after delivery showed a high incidence of seizures to auditory stimulation at the age of 4 months. The significant induction of c-fos mRNA by audiogenic seizures is prominent in several brain areas including central gray, peripeduncular nucleus, inferior colliculus, septal nucleus, bed nucleus of stria terminalis, and dorsomedial hypothalamus. However, the expression of c-fos mRNA was comparable in neocortex, dorsal hippocampus and medial geniculate body between control rats and PTU-treated, seizure-induced rats. These results confirm the previous report on the c-fos expression following audiogenic seizure sensitized during development by a loud noise [20]. The present results indicate that the neonatal PTU treatment may provide a useful tool for studying the mechanism underlying the seizure susceptibility and development after maturation.
Brain Res Mol Brain Res 1996 May
PMID:Expression of c-fos mRNA after audiogenic seizure in adult rats with neonatal hypothyroidism. 873 71

The repeated administration of the beta-carboline, FG 7142, to mice leads to 'chemical kindling', i.e., the development of seizures following doses which were initially insufficient to produce convulsive activity. Messenger RNA (mRNA) was prepared from the cortex of control and FG 7142-treated mice killed at 10-12 days or at 28-45 days after the last kindling injection, and this mRNA was injected into Xenopus oocytes. At 3-4 days following injection, a voltage clamp technique was used to record responses to kainic acid, gamma-aminobutyric acid (GABA), and N-methyl-D-aspartate (NMDA). Kainate was significantly more potent in oocytes expressing mRNA from kindled mice killed at either 10-12 or 28-45 days than in those injected with control mRNA. GABA also was more potent in oocytes with mRNA from kindled mice killed at 10-12 days, but this difference was not present at the longer interval. Chemical kindling did not change the response to NMDA. The current-voltage relation for kainate responses was linear, and plots from kindled and control mRNA were similar. The persistent increase in potency of kainate, an excitatory glutamate ligand, may play a role in producing the lowered FG 7142 threshold characteristic of kindled mice.
Brain Res Mol Brain Res 1996 Apr
PMID:Kainate, GABAA and NMDA receptors in Xenopus oocytes expressing mRNA from the cortex of mice kindled with FG 7142. 873 65

The effects of the intracerebroventricular (icv) and the intrahippocampal (ih) microinjection of the inorganic dye Ruthenium red (RuR) on motor activity, and the protective action of excitatory amino acid receptor antagonists and of GABAergic drugs, were studied in the rat. When administered icv, RuR produced intense tonic-clonic convulsions which were refractory to N-methyl-D-aspartate (NMDA) receptor antagonists and to diphenylhydantoin, whereas aminooxyacetic acid (AOA) and valproate only partially protected against seizure activity. The most notable motor effect of the ih RuR administration was the appearance of intense wet-dog shakes (WDS) behavior, which was remarkably attenuated by the icv or intraperitoneal (ip) administration of the NMDA receptor antagonists (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), CGP-37849, and MK-801, but not by their ih coinjection with RuR. Systemic AOA and valproate were also effective in reducing the number of WDS, whereas the non-NMDA receptor antagonist CNQX was ineffective. Light and electron microscopic observations of the RuR-injected brains revealed that the dye was highly concentrated in neuronal somas located in or near the injected areas. In the case of the CA1 region, remarkable damage of the pyramidal neurons was manifested by vacuolization, and 5-9 d after the injection notable cell loss and disruption of the CA1 cell layer organization was apparent. The results indicate that RuR penetrates selectively neuronal bodies and damage them, and suggest that the resulting motor alterations involve hyperactivity of glutamatergic neurotransmission.
Mol Chem Neuropathol 1995 Dec
PMID:Motor alterations and neuronal damage induced by intracerebral administration of Ruthenium red: effect of NMDA receptor antagonists and other anticonvulsant drugs. 874 30


<< Previous 1 2 3 4 5 6 7 8 9 10