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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of low or high (10 or 25 mM) K(+)-induced membrane depolarization on the mRNA levels for NMDA receptor subunits was investigated by RNase protection assay in cultured rat cerebellar granule cells. Cells, maintained for 7 days in K25+, a condition that promotes their survival and maturation, express the highest levels of NR-1 and NR-2A mRNA, whereas NR-2B is maximally expressed in cells grown in K10+. Acute changes in medium K+ concentration had a significant effect on the mRNA levels for NMDA receptor subunits. A concomitant reduction of NR-2A mRNA and induction of NR-2B was observed following a 24-h shift of the culture medium from K25+ to K10+. Under these circumstances NR-2C, not detected in basal conditions, became expressed. Neuronal nitric oxide synthase, an enzyme linked to NMDA receptor activation, was also influenced by growth conditions. Its expression, higher under low excitation (K10+), is induced in the shift from K25+ to K10+ and is markedly decreased in the opposite situation. These data indicate that several factors may influence the expression of NMDA receptor subunits and consequently may modulate the function of this receptor complex and its adaptation to acute and chronic changes in neuronal activity.
Brain Res Mol Brain Res 1996 Aug
PMID:Acute and chronic changes in K(+)-induced depolarization alter NMDA and nNOS gene expression in cultured cerebellar granule cells. 884 29

Although the psychological and physiological effects of nicotine have long suggested that nicotine exerts specific actions in the brain, the identification of neuronal nicotinic receptors (nAChRs) only began in the past few years with the development of molecular genetics. It is now clear that neuronal nAChRs form a family of highly heterogenous receptor subtypes, as evidenced by the number of genes encoding nAChR subunits, the diversity of immunopurified receptor proteins, and the multiple functional types of ligand-gated ion channels. Neuronal nAChRs have discrete localizations within the brain, and are involved in modulating neuronal firing and transmitter release. Cumulative evidence from animal and human studies indicates that nicotinic systems play a major role in higher cognitive functions and dysfunctions. In particular, the loss of cortical nAChRs is a neuro-chemical hallmark of Alzheimer (AD) and Parkinson (PD) diseases. In addition, nicotine improves memory and attention in Ad and PD. Our recent studies using electrophysiological biochemical and behavioral approaches suggest that the prefrontal cortex is a major target site for the cognitive actions of nicotine.
Mol Chem Neuropathol
PMID:Nicotinic receptors in the brain. Molecular biology, function, and therapeutics. 887 36

Neuronal cell death is both a vital component of the embryo-genesis of the nervous system and forms the basis of all neurodegenerative diseases. This overview explores the fundamental mechanisms underlying neuronal cell death at a cellular and molecular level. The significance of the mode of neuronal death is compared with respect to physiological (developmental) and pathological neuronal loss.
Mol Chem Neuropathol
PMID:Mechanisms of neuronal cell death. An overview. 887 53

Only recently have we become aware of the diversity of laminins in adult brain. In vascular basement membranes, the expression of at least five laminin chains has been demonstrated, suggesting the presence of several laminin variants. Recent ultrastructural evidence for heterogeneity of laminin expression in vascular basement membranes is an exciting finding, and points to structural and functional diversity of the basement membranes around cerebral blood vessels. Neuronal laminin-like immunoreactivity in the adult brain is a consistent observation, but does not fit well in the current understanding of the physiology and biochemistry of the heterotrimeric laminins. Nevertheless, the unique localization of putative neuronal laminins warrants their further characterization. The structure and function of laminins produced by reactive astrocytes in the lesioned adult brain and that seen in the brains of Alzheimer disease (AD) patients are not yet resolved. The possibility that these laminins play an important role in the CNS response to injury and pathophysiology of AD is expected to be a fruitful investigation. The next decade should see very significant advances in the characterization of brain laminins and, hopefully, in the elucidation of functional correlates to the structural diversity of laminins in brain.
Mol Chem Neuropathol
PMID:Laminins in the adult and aged brain. 887 61

Neuronal nitric oxide synthase (nNOS) mRNA levels and NADPH diaphorase (NADPH-d) staining were compared in the frontal cortex, visual cortex and hippocampus (dentate gyrus and CA subfields of Ammon's horn) of five Alzheimer's disease (AD) and six control brains. The cellular abundance of nNOS mRNA was quantified by in-situ hybridisation using 35S-labelled antisense oligonucleotides complementary to the human nNOS sequence. Although the mean level of nNOS expression was decreased in all three regions in AD cases as compared to controls, it did not reach significance. Neurones positively labelled for nNOS mRNA and neurones positive for NADPH-d histochemistry displayed similar distribution in control and AD cases. In AD brains the density of neurones having detectable levels of nNOS mRNA was significantly decreased in the white matter underlying the frontal cortex (P < 0.05) but not in the frontal cortex gray matter; no change was observed in the gray or white matter of the visual cortex in AD. The number of cells expressing detectable levels of nNOS mRNA in the hippocampus was also significantly decreased (P < 0.05) in AD. The density of NADPH-d-positive cells was not significantly decreased in the gray or white matter of the frontal or visual cortices in AD compared to controls; however, the number of NADPH-d-positive cells was significantly decreased in the hippocampus (P < 0.01). These data indicate that although the cellular abundance of nNOS mRNA is not significantly decreased in these three regions in AD, there is a significant decrease in the number of cells expressing detectable levels of nNOS mRNA in the white matter underlying the frontal cortex and in the dentate gyrus and CA subfields of the hippocampus in AD. Furthermore, there was also a significant decrease in the number of NADPH-d-positive cells in the dentate gyrus and CA subfields of the hippocampus in AD as compared to controls. These results suggest specific populations of nNOS/NADPH-d cells in the white matter underlying the frontal cortex and in the hippocampus are vulnerable in AD. The implications of these findings are discussed.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Neuronal nitric oxide synthase (nNOS) mRNA expression and NADPH-diaphorase staining in the frontal cortex, visual cortex and hippocampus of control and Alzheimer's disease brains. 888 32

This study is a follow-up of previous work which demonstrated that cultured cortical neurons did not synthesize HSP70i immediately after heat stress when compared with cultured cortical astrocytes. We have extended the period of observation for HSP70i induction of cultured cortical neurons and astrocytes up to 24 h after heat stress. Cultured rat cortical neurons derived from 16-day-old fetal rats respond differently to heat stress than cultured rat astrocytes derived from newborn rats. They showed a delayed HSP70i induction in the majority of cultured neurons and the response was heterogeneous and was absent in most smaller neurons. The delayed neuronal induction was accompanied by a prolonged activation of heat-shock transcription factor 1 (HSF-1) and prolonged transcription of HSP70i mRNA. In comparison astrocytes showed a marked early induction of HSP70i mRNA and protein. In addition the induction of HSP70i in astrocytes was followed by translocation of the protein into the nucleus, a finding which we failed to demonstrate in neurons. Immunostaining for HSP70i was more uniform in astrocytes than neurons. Many neurons did not stain for up to 24 h after heat shock in this study. Immunocytochemical staining of HSF-1 and 2 showed major differences between neurons and astrocytes. Astrocytes showed localization of HSF-1 to the nucleus before and after heat stress, while neurons showed HSF-1 localization to the cytoplasm and nucleus before and after heat stress. Finally HSF-2 was undetectable in neurons when compared with astrocytes by Western immunoblot analysis. However, astrocytes and neurons revealed weak immunostaining of HSF-2 in the cytoplasm and nucleus. The staining in the neurons was likely secondary to cross-reactivity to an unidentified protein. We conclude that HSP70i expression after heat shock is delayed in rat cortical neurons when compared with rat cortical astrocytes. In addition most small neurons did not synthesize HSP70i after heat shock. This difference in induction of HSP70i may be secondary to localization and activation of HSF-1 but not HSF-2. Neuronal susceptibility to injury may be related to the delayed induction of HSP70i and also the possible failure of newly synthesized HSP70i to translocate into the nucleus.
Brain Res Mol Brain Res 1996 Mar
PMID:Evidence for different mechanisms of induction of HSP70i: a comparison of cultured rat cortical neurons with astrocytes. 896 43

Marked concentration differences of noradrenaline (NA) between the vascular and the interstitial compartment were detected by sampling interstitial transudate from isolated perfused rat hearts. The ratios of vascular/interstitial concentration amounted to 7.4 to 1.3 depending on the concentration of NA administered (3 x 10(-9) to 10(-6) M). These concentration differences were abolished by inhibitors of uptake1 [desipramine (DMI)] and uptake2 (O-methyl-isoprenaline (OMI)). Neuronal uptake1 was characterized by a Km of 0.22 mumol/l and a Vmax of 370 pmol x min-1 x gWWT-1, extraneuronal uptake2 by a KUPTAKE of = 0.313 min-1. The apparent permeability surface area (P x S)-product calculated from uptake rate and transcapillary concentration difference was significantly decreased by administrating 100 mumol/l (NA) in presence of DMI. A presumed endothelial uptake mechanism contributing to catecholamine translocation was investigated in endothelial cells in culture. These cells showed a specific noradrenaline uptake with a K(m) of 4.35 mumol/l and a Vmax of about 75 pmol x min-1 x gWWT-1. Any inhibition by inhibitors of both of the two noradrenaline uptakes was lacking. The uptake rate of this mechanism is insufficient to contribute to the diffusive conductivity of the capillary wall (P x S-product). We conclude from our investigations on interstitial concentrations of catecholamines and transcapillary concentration differences, that the capillary wall, owing to its metabolic and diffusional characteristics, influences the exchange of catecholamines to a substantial and physiologically relevant extent.
Mol Cell Biochem
PMID:Interstitial noradrenaline concentration of rat hearts as influenced by cellular catecholamine uptake mechanisms. 897 54

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.
Brain Res Mol Brain Res 1997 Feb
PMID:Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. 903 Jul 7

Neuronal death occurs naturally during brain development and is a common response to an external insult. Cell death, whose mechanisms are currently being elucidated, appears in three forms: necrosis, apoptosis and programmed cell death. Recently, attention has focused on a family of cysteine proteases whose prototype is interleukin-1 beta converting enzyme (ICE). ICE, essential for IL-1 beta production and, thus, critical to necrotic mechanisms, also plays a role in apoptosis mediated through the stimulation of the lymphocyte fas antigen. The absence of ICE expression in neurons makes ICE an unlikely direct participant in neuronal death. However, the existence of ICE family members in neurons combined with the pharmacological inhibition of both apoptosis in vitro and programmed cell death during development make ICE homologs candidates for mediating these two forms of cell death. Since several neurodegenerative diseases as well as at least one neurological disorder may have an apoptotic component, antagonists of this protease family may be neuroprotective.
Mol Psychiatry 1996 Mar
PMID:Watch for ICE in neurodegeneration. 911 18

Neuronal Cdk5 activator (Nck5a) differs from other cyclin-dependent kinase (Cdk) activators in that its amino acid sequence is only marginally similar to the cyclin consensus sequence. Nevertheless, computer modeling has suggested that Nck5a contains the cyclin-fold motif recently identified in the crystal structure of cyclin A. In the present study, a number of truncation mutants and substitution mutants of the Nck5a were produced and tested for the Cdk5 activation and Cdk5 binding activity. The active domain of Nck5a determined by using the truncation mutants consists of the region spanning residues 150 to 291. The size of Nck5a active domain is essentially the same as that of cyclin A required for Cdk2 activation (Lees, E. M., and Harlow, E. (1993) Mol. Cell. Biol. 13, 1194-1201). The change, or the lack of change, in Cdk5 activation activity observed with a number of substitution mutants may be understood on the basis of structure and function relationship of cyclin A. These results provide support to the previous suggestion (Brown, N. R., Noble, M. E. M., Endicott, J. A., Garman, E. F., Wakatsuki, S., Mitchell, E., Rasmussen, B., Hunt, T., and Johnson, L. N. (1995) Structure 3, 1235-1247) that the activation domain of Nck5a adopts a conformation similar to that of cyclin A. They also provide a partial answer to the question of how Nck5a, a non-cyclin, activates a cyclin-dependent kinase.
 ...
PMID:Cyclin-dependent kinase 5 (Cdk5) activation domain of neuronal Cdk5 activator. Evidence of the existence of cyclin fold in neuronal Cdk5a activator. 913 76


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