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)

Neuronal death, secondary to endogenous agents such as glutamate, may involve changes in cytoplasmic calcium. Besides its well recognized role as a second messenger mediating cellular response, calcium is necessary for the activation of endonuclease(s), resulting in DNA fragmentation and cell death. Therefore, we investigated the relationship between changes in cytoplasmic calcium, DNA fragmentation and neuronal death, using PC12 and NCB-20 cell lines. The calcium ionophore, A23187, caused a dose-dependent increase in cytoplasmic calcium, loss of cell viability, increased lactate dehydrogenase (LDH)-release, and DNA fragmentation. DNA fragments, typical of internucleosomal digestion of genomic DNA, characteristic of endonuclease(s) activation, were consistently detected in the incubating medium. Release of DNA fragments into the medium was seen with A23187 in concentrations as low as 10 nM, and within an hour of treatment. Furthermore, calcium added to preparations of PC12 nuclei also produced DNA fragmentation, although, less pronounced than when intact cells were treated with A23187. The findings indicate that A23187-induced neuronal death involves the activation of endonuclease(s). The role of cytoplasmic calcium in this process is supported by evidence that A23187 selectively mobilizes cytoplasmic calcium, and that calcium can directly activate endonuclease(s) in nuclear preparations.
Brain Res Mol Brain Res 1993 Jan
PMID:Neuronal death, cytoplasmic calcium and internucleosomal DNA fragmentation: evidence for DNA fragments being released from cells. 838 11

Neuronal/nicotinic alpha-bungarotoxin binding sites (nBgtS) found in the nervous system are not well characterized. In this study, photolabile toxin derivatives have been used in affinity labeling protocols to investigate the subunit composition of nBgtS expressed by different neuron-like cell lines. Data obtained was compared to the known subunit composition of toxin-binding muscle-type nicotinic acetylcholine receptors (nAChR). Muscle-type nAChR-rich membranes prepared from Torpedo electroplax contain components with corrected apparent molecular sizes of 41, 46, 50, 62 and 66 kDa that are reactive with toxin. The photoaffinity labeling patterns for preparations derived from cells of the TE671 clone, which express muscle-type nAChR, are very similar to that of cells of the IMR-32 or SH-SY5Y clonal lines, which express nBgtS. There is consistent labeling of four polypeptides with corrected apparent molecular weights of 40, 43, 47 and 56 kDa. These results suggest that both mammalian muscle-type nAChR and mammalian nBgtS are similarly composed of at least four kinds of subunits.
Brain Res Mol Brain Res 1993 Jan
PMID:Photoaffinity labeling of muscle-type nicotinic acetylcholine receptors and neuronal/nicotinic alpha-bungarotoxin binding sites with a derivative of alpha-bungarotoxin. 838 15

Localization of the alpha 2 macroglobulin receptor (alpha 2MR) was studied in postmortem human brain tissue of Alzheimer disease (AD) and age-matched control cases with a monoclonal antibody (A2MR alpha 2) to the receptor. In control cases alpha 2MR was detected in neurons, glia, and some capillaries. Neuronal staining was most conspicuous in the hippocampus and entorhinal cortex. In AD, alpha 2MR immunoreactivity was enhanced. The staining intensity of some neurons was increased, as was the number of positive glial cells. In addition, senile plaques, tangles, and dystrophic neurites were strongly stained. These results suggest that alpha 2MR is involved in AD pathology.
Mol Chem Neuropathol
PMID:Immunohistochemical study of alpha 2 macroglobulin receptor in Alzheimer and control postmortem human brain. 846 89

Neuronal cdc2-like kinase, nclk, is a heterodimer of cyclin dependent protein kinase 5, cdk5, and a 25 kDa subunit derived from a novel, neuron-specific, 35 kDa protein: p35. The characterization and regulation of nclk will be summarized in this minireview. The activity of nclk appears to be governed by highly complex regulatory mechanisms including protein-protein interaction, protein phosphorylation and isoforms. The histone H1 kinase activity of nclk is absolutely dependent of the interaction between the 25 kDa subunit and the catalytic subunit, cdk5. In addition, nclk interacts with other cellular proteins to form macromolecular complexes. The kinase activity of nclk is inhibited in vitro by the phosphorylation reactions of a weel-like protein tyrosine kinase and a protein serine/threonine kinase from bovine thymus. Northern blot analysis has revealed the existence of two populations of p35 mRNA of 2 and 4 kb. A novel cDNA encoding a p35 homologous protein has been obtained from a human hippocampus library.
Mol Cell Biochem
PMID:Regulatory properties of neuronal cdc2-like kinase. 856 47

Neuronal differentiation involves extensive rearrangement of the cytoskeleton, including the actin-based microfilament system, and establishment of molecular compartments within the neuron. The intracellular distribution of tropomyosin (Tm) mRNA in vivo and in vitro has been examined and correlated with protein targetting. The mRNAs encoding two Tm isoforms were found to be differentially localized in developing neurons. Tm-5 mRNA is localized to the axonal pole of differentiating embryonic rat neurons, in contrast to TmBr-2 mRNA distribution throughout the cell body. Tm-5 mRNA is transported into the axon of differentiating primary cultured neurons. This mRNA localization is developmentally regulated and correlates with the targeting of Tm-5 protein to growing axons. Tm-5 colocalizes with a subset of neuronal microfilaments associated with the initiation and maintenance of outgrowth. The segregation of Tm-5 is the earliest known marker of neuronal polarity and may play a role in the establishment of polarity.
Mol Cell Neurosci 1995 Oct
PMID:Intracellular localization of tropomyosin mRNA and protein is associated with development of neuronal polarity. 858 12

It is well established that leucine-rich repeat (LRR) proteins such as connectin, slit, chaoptin, and Toll have pivotal roles in neuronal development in Drosophila as cell adhesion molecules. However, to date, little information concerning mammalian LRR proteins has been reported. In the present study, we sought LRR proteins of the mouse brain, based on the assumption that fundamental mechanisms are conserved between different species. We screened a neonatal mouse brain cDNA library with a human partial cDNA encoding LRR protein as a probe. We obtained two independent cDNAs encoding LRR proteins, designated NLRR-1 and NLRR-2 (Neuronal Leucine-Rich Repeat proteins). We analyzed the whole sequence of NLRR-1 and partial sequence of NLRR-2. Sequence analysis showed that these two clones are about 60% homologous to each other, and that NLRR-1 protein is a transmembrane protein. Northern blot analysis and in situ hybridization histochemistry showed that both NLRR-1 and NLRR-2 mRNAs were expressed primarily in the central nervous system (CNS); NLRR-1 mRNA was also detected in the non-neuronal tissues such as cartilage, while NLRR-2 mRNA expression was confined to the CNS at all developmental stages. These results suggest that there is at least one LRR protein family in the mouse and that these molecules may play significant but distinct roles in neural development and in the adult nervous system.
Brain Res Mol Brain Res 1996 Jan
PMID:Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system. 871 37

Neurotrophins are profound regulators of neuronal survival in the developing peripheral nervous system and are synthesized by peripheral neurons themselves both during development and in maturity. Neuronal neurotrophin expression may be importantly related to survival of mature neurons, both in normal and pathological states. We show here that brain-derived neurotrophic factor (BDNF) gene expression in dorsal root ganglia is strongly stimulated in vivo by another neurotrophin, nerve growth factor (NGF). Furthermore, colocalization studies show that many BDNF-expressing sensory neurons also express trk A, the high-affinity NGF receptor. These results demonstrate a novel regulatory mechanism for neurotrophin gene expression and suggest a paracrine function for neurotrophins in mature animals.
Mol Cell Neurosci 1996 Feb
PMID:Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. 873 81

Neuronal thread proteins (NTPs) are a family of developmentally regulated molecules expressed in central nervous system (CNS) neurons and primitive neuroectodermal tumor (PNET) cell lines. NTP gene expression is modulated with DNA synthesis, neuritic sprouting, and neuronal differentiation. The present study explores the mechanism of insulin modulation of NTP gene expression during neuronal differentiation using PNET cell lines of CNS origin. PNET2 cells underwent neuronal differentiation with neurite outgrowth coupled with transient up-regulation of several species of NTP. In contrast, PNET1 cells failed to differentiate in response to insulin stimulation, although insulin receptors were more abundant than in PNET2 cells. Analysis of the insulin-mediated signal transduction pathway demonstrated that the lack of insulin responsiveness in PNET1 cells was primarily caused by impaired insulin-mediated tyrosyl phosphorylation of the insulin receptor substrate-1 (IRS-1). Correspondingly, the association between phosphatidyl-inositol 3 (PI3) kinase and phosphorylated IRS-1 was reduced in PNET1 compared with PNET2 cells. In contrast, the levels of IRS-1 protein were similar in PNET1 and PNET2 cells, and expression of the insulin receptor beta subunit (Ir beta) and insulin-mediated tyrosyl phosphorylation of the Ir beta were greater in PNET1 than PNET2 cells. The findings suggest that insulin effected neuronal differentiation and modulation of NTP gene expression in PNET cells utilizes a signal transduction cascade that requires tyrosyl phosphorylation of IRS-1.
J Mol Neurosci 1995
PMID:Insulin-induced differentiation and modulation of neuronal thread protein expression in primitive neuroectodermal tumor cells is linked to phosphorylation of insulin receptor substrate-1. 874 48

Spinal muscular atrophy is an autosomal recessive disorder which affects about 1 in 10,000 individuals. The three clinical forms of SMA were mapped to the 5q13 region. Three candidate genes have been isolated and shown to be deleted in SMA patients: the Survival Motor Neuron gene (SMN), the Neuronal Apoptosis Inhibitory Protein gene (NAIP) and the XS2G3 cDNA. In this report we present the molecular analysis of the SMN exons 7 and 8 and NAIP exon 5 in 65 Spanish SMA families. NAIP was mostly deleted in type I patients (67.9%) and SMN was deleted in 92.3% of patients with severe and milder forms. Most patients who lacked the NAIP gene also lacked the SMN gene, but we identified one type II patient deleted for NAIP exon 5 but not for SMN exons 7 and 8. Two other patients carried deletions of NAIP exon 5 and SMN exon 7 but retained the SMN exon 8. Three polymorphic variants from the SMN gene, showing changes on the sequence of the centromeric (cBCD541) and telomeric copies of the SMN gene, were found. In addition, we show several genetic rearrangements of the telomeric SMN gene, which include duplication of this gene in one normal chromosome, and putative gene conversion events in affected and normal chromosomes. Altogether these results corroborate the high genetic variability of the SMA region. Finally, we have determined the ratio between the number of centromeric and telomeric copies of the SMN gene in parents of SMA patients, showing that the majority of parents of types II and III patients carried three or more copies of the cBCD541 gene; we suggest a relationship between the number of copies of cBCD541 and the disease phenotype.
Hum Mol Genet 1996 Feb
PMID:Molecular analysis of the SMN and NAIP genes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype. 882 82

We previously reported that the total neurotrophic activity of hippocampal extracts was significantly (25-50%) reduced after 21-28 weeks of chronic ethanol treatment (CET) [23]. To test whether the level of a neurotrophic factor (i.e., ligand itself) is compromised, we measured nerve growth factor (NGF) protein and NGF mRNA contents using ELISA and Northern analysis. We reported that CET did not appear to reduce NGF protein, NGF mRNA or total neurotrophic activity when measured on sympathetic ganglia neurons [4]. We also observed that both NT-3 mRNA and bFGF mRNA levels were unaffected, but the BDNF mRNA levels was significantly reduced in CET rat hippocampus [18]. Neuronal degeneration and reduction of total neurotrophic activity after CET appear to be induced, at least partially, by compromised transcription of BDNF gene. CET may also induce functional changes in receptors for the neurotrophic factors. To investigate possible changes in neurotrophic factor-receptors, we examined Western blots (immunoblots) of rat cortex after 28 weeks of CET. After sonication and ultra-centrifugation, the supernatant of crude lysates of the cortex from individual animals was subjected to SDS-PAGE, electrotransfered to nitrocellulose membrane, incubated with anti-trk B antibody and secondary antibody conjugated to alkaline phosphatase, and reacted with chemiluminescent substrate. The membranes were then exposed to Kodak XAR film. Compared to controls (n = 6), CET rats (n = 6) appeared to have significantly higher band intensity (P < 0.01) of trk B-like protein at about 145 kDa, which suggests an up-regulation of trk B-like proteins to compensate the compromised level of certain subset (i.e., BDNF or NT-4/5, but not NGF) of neurotrophins in cortex.
Brain Res Mol Brain Res 1996 Aug
PMID:Up-regulation of high-affinity neurotrophin receptor, trk B-like protein on western blots of rat cortex after chronic ethanol treatment. 884 27


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