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)

The present minireview describes experiments carried out, in short-term crush-operated rat nerves, using immunofluorescence and cytofluorimetric scanning techniques to study endogenous substances in anterograde and retrograde fast axonal transport. Vesicle membrane components p38 (synaptophysin) and SV2 are accumulating on both sides of a crush, but a larger proportion of p38 (about 3/4) than of SV2 (about 1/2) is recycling toward the cell body, compared to the amount carried with anterograde transport. Matrix peptides, such as CGRP, ChRA, VIP, and DBH are recycling to a minor degree, although only 10-20% of surface-associated molecules, such as synapsins and kinesin, appear to recycle. The described methodological approach to study the composition of organelles in fast axonal transport, anterograde as compared to retrograde, is shown to be useful for investigating neurobiological processes. We make use of the "in vivo chromatography" process that the fast axonal transport system constitutes. Only substances that are in some way either stored in, or associated with, transported organelles can be clearly observed to accumulate relative to the crush region. Emphasis in this paper was given to the synapsins, because of diverging results published concerning the degree of affiliation with various neuronal organelles. Our previously published results have indicated that in the living axons the SYN I is affiliated with mainly anterogradely fast transported organelles. Therefore, some preliminary, previously unpublished results on the accumulations of the four different synapsins (SYN Ia, SYN Ib, SYN IIa, and SYN IIb), using antisera specific for each of the four members of the synapsin family, are described. It was found that SYN Ib clearly has a stronger affiliation to anterogradely transported organelles than SYN Ia, and that both SYN IIa and SYN IIb are bound to some degree to transported organelles.
Mol Neurobiol
PMID:Organelles in fast axonal transport. What molecules do they carry in anterograde vs retrograde directions, as observed in mammalian systems? 128 29

In the present study 61 male pesticide applicators who worked in cotton fields and regularly sprayed pesticides such as DDT, BHC, endosulfan, malathion, methyl parathion, phosphamidon, dimethoate, monocrotophos, quinalphos fenvelrate, and cypermethrin were analyzed for sister chromatid exchanges, mitotic index, and cell cycle kinetics in peripheral lymphocytes. Subjects who handled pesticides were non-smokers and teetotalers and the data were compared with the matched control group. Statistical analysis revealed that the frequency of sister chromatid exchanges was significantly higher among the pesticide applicators at all the durations of exposure when compared to controls. Subjects exposed to pesticides also showed cell cycle delay and decrease in mitotic index when compared to the control group.
Environ Mol Mutagen 1991
PMID:Frequency of sister chromatid exchange in peripheral lymphocytes of male pesticide applicators. 187 5

Heteronuclear 2D and 3D NMR experiments were carried out on recombinant Drosophila calmodulin (CaM), a protein of 148 residues and with molecular mass of 16.7 kDa, that is uniformly labeled with 15N and 13C to a level of greater than 95%. Nearly complete 1H and 13C side-chain assignments for all amino acid residues are obtained by using the 3D HCCH-COSY and HCCH-TOCSY experiments that rely on large heteronuclear one-bond scalar couplings to transfer magnetization and establish through-bond connectivities. The secondary structure of this protein in solution has been elucidated by a qualitative interpretation of nuclear Overhauser effects, hydrogen exchange data, and 3JHNH alpha coupling constants. A clear correlation between the 13C alpha chemical shift and secondary structure is found. The secondary structure in the two globular domains of Drosophila CaM in solution is essentially identical with that of the X-ray crystal structure of mammalian CaM [Babu, Y., Bugg, C. E., & Cook, W.J. (1988) J. Mol. Biol. 204, 191-204], which consists of two pairs of a "helix-loop-helix" motif in each globular domain. The existence of a short antiparallel beta-sheet between the two loops in each domain has been confirmed. The eight alpha-helix segments identified from the NMR data are located at Glu-6 to Phe-19, Thr-29 to Ser-38, Glu-45 to Glu-54, Phe-65 to Lys-77, Glu-82 to Asp-93, Ala-102 to Asn-111, Asp-118 to Glu-127, and Tyr-138 to Thr-146. Although the crystal structure has a long "central helix" from Phe-65 to Phe-92 that connects the two globular domains, NMR data indicate that residues Asp-78 to Ser-81 of this central helix adopt a nonhelical conformation with considerable flexibility.
 ...
PMID:Secondary structure and side-chain 1H and 13C resonance assignments of calmodulin in solution by heteronuclear multidimensional NMR spectroscopy. 190 92

The expression of mRNA for the calmodulin-dependent form of brain nitric oxide synthase (NOS) was examined in cholinergic cells of the rat brain using a method combining in situ hybridization histochemistry with immunocytochemistry for choline acetyltransferase (ChAT) in the same brain sections. We constructed a riboprobe specific for brain NOS by subcloning a 493 bp fragment of the coding region which displayed low homology to other forms of NOS. The general distribution of NOS mRNA was in excellent agreement with previous studies using the full-length probe or NADPH diaphorase histochemistry. NOS mRNA was observed in many brain structures and relative levels were quantitated using grain counting procedures in a number of cholinergic and non-cholinergic neuronal groups throughout the brain. In the forebrain, ChAT-immunoreactive cells or cell groups were observed in medial septum (MS), vertical limbs of diagonal band (DBV) and horizontal limbs of diagonal band (DBH), nucleus basalis magnocellularis (NBM), substantia innominata (SI), and striatum (ST). In the brainstem, the cholinergic groups studied included those located in the pedunculopontine tegmental nucleus (PPTN), the laterodorsal tegmental nucleus (LDTN), the nucleus parabigeminalis and several motor nuclei. For NOS mRNA quantitation, silver grains overlying ChAT-stained neuronal profiles in sections on emulsion-dipped slides were counted digitally. In the LDTN and PPTN, virtually all the ChAT-positive cells expressed NOS mRNA at high levels. In MS, DBV and SI, about 30-50% of the ChAT-positive cells expressed NOS mRNA at low-to-moderate levels. Less than 20% of ChAT-positive neurons in the other cholinergic populations studied expressed NOS mRNA; the NBM was one of these low-expressing populations. Many scattered non-cholinergic cells expressing NOS mRNA were found in the striatum and cerebral cortex. In other non-cholinergic regions, high NOS mRNA expression was observed in the islands of Calleja, thalamic and hypothalamic nuclei, several amygdaloid nuclei, regions related to the optic tract, the interpeduncular nucleus, and the supramammillary nucleus. The heterogeneous distribution of NOS mRNA implies complex roles for nitric oxide neurotransmission in brain function, including for the cholinergic phenotype. Additionally, given the postulated involvement of nitric oxide in neurodegeneration, the widely varying levels of expression of NOS within identified central cholinergic neurons may relate to differential vulnerability of this phenotype in disease or aging.
Brain Res Mol Brain Res 1994 Apr
PMID:Nitric oxide synthase gene expression in cholinergic neurons in the rat brain examined by combined immunocytochemistry and in situ hybridization histochemistry. 751 28

Antigenic stimulation of rat basophilic leukemia cells releases Ca2+ from internal stores and increases membrane permeability to Ca2+. The delta isomer of hexachlorocyclohexane (delta-HCH) is structurally similar to myo-inositol-1,4,5-trisphosphate (IP3) and is a potent releaser of stored Ca2+ from permeabilized cells. This release of Ca2+ is not mediated by a competitive interaction with the IP3 receptor on the Ca2+ release channel on the endoplasmic reticulum. In intact cells, delta-HCH and, to a lesser extent, lindane (gamma-hexachlorocyclohexane) transiently increase the intracellular Ca2+ concentration. The return to basal concentrations is mediated by the plasma membrane Ca2+ pumps and not by resequestration of Ca2+ into intracellular stores. Treatment of cells with delta-HCH (25-100 microM), but not lindane, leads to a progressive inhibition of the antigen- and thapsigargin-stimulated Ca2+ signal. Caffeine, a modulator of the ryanodine receptor Ca2+ channel, attenuates the rise in intracellular Ca2+ induced by delta-HCH, suggesting that ryanodine receptor-like Ca2+ channels may be present in RBL cells. At 25 microM delta-HCH, a concentration that does not inhibit the antigen-stimulated Ca2+ signal, the release of [3H]serotonin from antigen-stimulated cells is enhanced as is secretion of [3H]serotonin from cells pretreated with 25-100 microM lindane. The depletion of Ca2+ from intracellular stores by delta-HCH should evoke Ca2+ entry into the cells by a capacitative mechanism; however; divalent cation permeability across the plasma membrane (Mn2+ influx) is not increased but rather is decreased by delta-HCH. An understanding of the mechanism of action of delta-HCH in releasing stored Ca2+ and blocking Ca2+ influx across the plasma membrane may provide insights into the regulation of capacitative Ca2+ entry in nonexcitable cells.
Mol Pharmacol 1995 Sep
PMID:The delta isomer of hexachlorocyclohexane induces rapid release of the myo-inositol-1,4,5-trisphosphate-sensitive Ca2+ store and blocks capacitative Ca2+ entry in rat basophilic leukemia cells. 756 33

We have previously demonstrated allele loss in hamartomas from patients with tuberous sclerosis for markers spanning the tuberous sclerosis gene on chromosome 16q13.3 (TSC2). Germline deletions in the TSC2 gene have been shown in 5% of patients with tuberous sclerosis (TSC). These data support our hypothesis that the TSC2 gene acts as a growth suppressor gene, analogous to the traditional tumour suppressor gene. We now report a TSC hamartoma showing allele loss for markers on chromosome 9q34 in the region of the TSC1 gene. We studied six hamartomas from four sporadic and two familial cases of TSC, none of which showed allele loss for markers on chromosome 16p13.3. The hamartomas were paraffin embedded sections of three renal angiomyolipomas, two giant cell astrocytomas, and a cardiac rhabdomyoma. Eight markers were analysed, comprising from centromeric to telomeric ASS-D9S64-D9S149-ABO-D9S150-DBH-D9S66-D9S67++ +. One angiomyolipoma showed allele loss for the markers ABO, DBH and D9S66, but not for D9S149 or D9S67. The patient was not informative for D9S150. The family structure did not permit the phase of the disease and marker alleles to be determined. These finding support the hypothesis that the TSC1 gene on 9q34, like the TSC2 gene, acts as a growth suppressor. The data would place the TSC1 gene between D9S149 and D9S67. Mapping of allele loss in hamartomas may help in the refinement of the location of the TSC1 locus.
Hum Mol Genet 1994 Oct
PMID:The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor. 784 9

Reserpine treatment was used to examine whether short- and long-term neural stimulation regulates rat adrenal medullary dopamine beta-hydroxylase (DBH, EC 1.14.17.1) through transcriptional activation and to examine the extent of coordinate control of DBH and phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). A single dose of reserpine (10 mg/kg i.p.) elevates DBH mRNA 1.5-fold by 6 h post-injection. Chronic treatment (10 mg/kg i.p., 4 alternate day injections) continues the rise in DBH mRNA, with a peak of 3.4-fold control values after 2 doses of reserpine and a plateau at this level thereafter. Even though DBH mRNA is elevated 6 h after a single injection of reserpine, DBH activity does not change in parallel. A 1.3-fold rise in activity occurs at 24 h post-injection. In contrast, chronic reserpine treatment concomitantly increases DBH activity and mRNA. As observed for DBH mRNA, enzyme activity peaks and plateaus after 2 injections on alternate days. However, the rise in enzymatic activity is less than the rise in mRNA (2.4-fold versus 3.4-fold). Ribosomal loading experiments demonstrate that the DBH mRNA pool is fully utilized for protein synthesis with an apparent decrease in the number of ribosomes loaded per molecule of mRNA. Western analysis and thermal denaturation studies indicate that an altered form of DBH may be expressed. With a single dose of reserpine, the enzyme shows a decline in specific activity while repeated treatment leads to an enzyme with higher specific activity. In both cases, the protein appears to be more stable. Reserpine treatment also markedly elevates adrenal glucocorticoids. A 1.5-fold increment in glucocorticoid receptor mRNA accompanies the corticosteroid rise, with the receptor mRNA peaking at 6 h and remaining at this level thereafter. The up-regulation of glucocorticoid receptor mRNA expression, together with the presence of a putative glucocorticoid response element in the 5' flanking region of the DBH gene, suggests that neural and hormonal regulatory mechanisms may work in concert to control DBH gene transcription. Finally, by comparison to PNMT, activation of DBH appears to require sustained stimulation of the neural axis, since acute changes in mRNA lead to only minor changes in enzyme expression. Similar to PNMT, continuous neural stimulation increases both DBH mRNA and enzymatic activity. However, the discordance in the magnitude of these indices suggests that other regulatory controls may be important in setting the ultimate limits on DBH expression, glucocorticoids perhaps being one such influence.
Brain Res Mol Brain Res 1994 Aug
PMID:Neural control of dopamine beta-hydroxylase in vivo: acute and chronic effects. 798 52

Backbone 1H, 13C, and 15N NMR assignments were obtained for the complex of chicken muscle adenylate kinase (AK) with its bisubstrate analog, MgAP5A [magnesium P1,P5-bis(5'-adenosyl)-pentaphosphate]. The assignments were used to elucidate the secondary structures and the enzyme-MgAP5A interactions. The work involves two unusual features: the molecular weight of AK (21.6 kDa) is one of the largest, on a monomeric basis, for which nearly complete assignment has been reported to date, and the assignment was performed at pH 7.1 instead of the acidic pH used for most other proteins. The results are summarized as follows. Firstly, unambiguous sequential assignments of backbone resonances have been achieved effectively by the combined use of two sequential assignment methods: NOE-directed assignments and the recently developed 1J-coupling-directed assignments. The starting points of the assignments were provided by several specifically labeled enzyme samples. Over 90% of the backbone 1H, 13C, and 15N resonances have been assigned. Secondly, spin system information was obtained from the HCCH-TOCSY and HCCH-COSY experiments as well as from 2D homonuclear NMR data. Overall, the side-chain resonances of ca. 40% of the residues, including most of the those displaying NOEs with the adenosine moieties of MgAP5A, have been assigned. Thirdly, secondary structural elements in the AK-MgAP5A complex were identified by extensive analyses of 1H-15N 2D HMQC-NOESY and 3D NOESY-HMQC spectra. Overall, the enzyme consists of ca. 60% alpha-helices and a five-stranded parallel beta-sheet. The results are compared with the secondary structure of the free AK from porcine muscle in crystals [Dreusicke, D., Karplus, P. A., & Schulz, G. E. (1988) J. Mol. Biol. 199, 359-371]. Lastly, most of the intermolecular NOEs between AK and the adenosine moieties of MgAP5A have been identified: Thr39, Leu43, Gly64, Leu66, Val67, Val72, and Gln101 are in proximity to the adenosine moiety of the adenosine 5'-monophosphate site, whereas Thr23 is in proximity to that of the adenosine 5'-triphosphate site. These data are discussed in relation to previous results from site-directed mutagenesis, NMR, and X-ray studies and in relation to the mechanism of catalysis.
 ...
PMID:Mechanism of adenylate kinase. 1H, 13C, and 15N NMR assignments, secondary structures, and substrate binding sites. 824 Nov 42

An efficient method is presented for the assignment of the proton, carbon, and nitrogen resonances in the NMR spectra of isotopically labeled nucleic acids. The assignment strategy starts by identifying all protons and carbons belonging to the same sugar ring through application of a set of 2D or 3D heteronuclear HCCH NMR experiments. Next the individual sugar rings are connected to their corresponding bases through intra-residue 1H-1H nuclear Overhauser effects (NOEs) observed in a 3D (1H, 13C, 1H) NOESY-HMQC experiment. Sequential NOE connectivities observed in this experiment are then used to assign each residue in the nucleotide sequence. The imino protons and nitrogens, and the cytidine amino protons and nitrogens, are assigned by 2D (15N, 1H) HMQC and 3D (1H, 15N, 1H) NOESY-HMQC experiments in H2O. This assignment procedure is illustrated on the 99% 13C/15N labeled RNA duplex r(GGCGCUUGCGUC)2. The application of these multi-dimensional heteronuclear magnetic resonance experiments enormously simplifies the resonance assignment of nucleic acids and allows assignment of many more protons, carbons and nitrogens than was possible using standard techniques on unlabeled molecules. Since a larger percentage of the protons can now be assigned by these experiments, much more NMR structural information can be obtained which will significantly extend the size limit for solution structure determinations of RNAs.
J Mol Biol 1993 Aug 20
PMID:An efficient procedure for assignment of the proton, carbon and nitrogen resonances in 13C/15N labeled nucleic acids. 839 48

Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) catalyzes the conversion of dopamine to norepinephrine, the third step of catecholamine biosynthesis. We have previously created transgenic mice harboring a chimeric gene consisting of the 4-kb DNA fragment of the human DBH gene promoter and the human phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) cDNA, to express PNMT in norepinephrine- and epinephrine-producing cells in the brain, sympathetic ganglia, and adrenal medullary chromaffin cells (Kobayashi et al., Proc. Natl. Acad. Sci. U.S.A., 89 (1992) 1631-1635). In this paper, we produced for the first time the antibody that specifically detects human PNMT, but not mouse PNMT, with the synthetic oligopeptide characteristic of the human PNMT sequence, and used this antibody to investigate the cells expressing human PNMT in transgenic mice. Immunohistochemical analysis of transgenic mice showed typical expression of human PNMT immunoreactivity in norepinephrinergic and epinephrinergic neurons in brain, as well as norepinephrine- and epinephrine-producing cells in the adrenal gland, indicating that the 4-kb 5'-flanking region is essential for the tissue-specific expression of the DBH gene. We also detected the ectopic expression in some DBH-immunonegative cells in the olfactory bulb of transgenic mice.
Brain Res Mol Brain Res 1993 Mar
PMID:The 5'-flanking region of the human dopamine beta-hydroxylase gene promotes neuron subtype-specific gene expression in the central nervous system of transgenic mice. 851 Apr 98


1 2 3 4 5 6 7 8 Next >>