Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 102 brains obtained from patients with acquired immune deficiency syndrome (AIDS), 34 cases with subacute AIDS encephalitis were characterized by immunohistochemistry using an antibody that binds to a human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp41. This glycoprotein was detected in mononucleated and/or multinucleated cells in 90% of adult and 50% of pediatric brains with subacute AIDS encephalitis. In addition, many gp41-positive cells with bipolar or multipolar processes were found in 10 cases, and these cells occurred most frequently in the basal ganglia and internal capsule. The phenotype of the gp41-positive cells was determined using an improved double-labeling immunohistochemical technique that employed beta-galactosidase and peroxidase conjugated reagents. Cell-type specific markers for double-labeling included: Ricinus communis agglutinin-1 (RCA-1) for macrophages and microglia; Ulex europaeus agglutinin-1 for endothelium; anti-glial fibrillary acidic protein (GFAP) for astrocytes; anti-amyloid precursor protein for neurons; and anti-leukocyte common antigen for leukocytes. Results of double-immunostaining revealed that gp41-positive cells of all morphologic types, including cells with bipolar or multipolar processes, were double-labeled with RCA-1, but not with markers for astrocytes, neurons, or endothelia. These findings support the contention that HIV-1 infection of the CNS is predominantly restricted to cells of the macrophage/microglia lineage.
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PMID:Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. 169 70

The Escherichia coli lacZ gene was stably introduced into phi C31-based phage cloning vectors in Streptomyces lividans. However, lacZ could not be stably introduced into S. lividans on the plasmid vectors pIJ702 or pIJ41. Studies of the expression of lacZ in S. lividans and S. coelicolor were facilitated by the use of mutants and/or growth conditions in which endogenous beta-galactosidase activity was low or absent. Plaques and lysogens of phi C31::lacZ constructs involving transcriptional fusions to the pBR322 tet gene contained beta-galactosidase activity. Activities were markedly higher in S. lividans than in S. coelicolor. Insertion of the major transcriptional terminator of coliphage fd between the tet promoter and lacZ reduced lacZ expression more in lysogens than in lytically infected cultures, suggesting the existence of a phage-specified anti-termination function. Several phi C31 derivatives suitable for the construction of different kinds of transcriptional and translational fusions in Streptomyces were derived. The expression of lacZ in one transcriptional fusion vector (KC659) was increased both in plaques and in lysogens by the appropriately positioned insertion of a previously characterized promoter from the aph gene of S. fradiae. When phi C31 DNA fragments were inserted into KC659, at least one recombinant phage gave high beta-galactosidase activity in lytic infections, but not in lysogens. The potential usefulness of lacZ fusions in Streptomyces is discussed.
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PMID:The expression of the Escherichia coli lacZ gene in Streptomyces. 302 36

To express high levels of proteins encoded by transfected DNA constructs in a variety of cultured cells, including neuronal cells, the activities of nine different promoters were evaluated using Escherichia coli beta-galactosidase (beta-gal) (LacZ) as a reporter gene. These nine promoters were categorized into three distinct groups (high, intermediate, and low expresser), in terms of the levels of beta-gal expression. An expression vector containing the cytomegalovirus enhancer and the chick beta-actin promoter (high expresser) showed the highest levels of expression, followed by vectors containing the cytomegalovirus promoter/enhancer and the SV40 promoter/enhancer (intermediate expresser). The rest of the promoters (thymidine kinase, adenovirus, murine proliferative sarcoma virus, nerve growth factor receptor, Rous sarcoma and mouse mammary tumor virus, and beta-amyloid precursor protein) expressed low levels of beta-gal. These results were consistent for eight different cell types. A particularly attractive model is the stem cell, P19; cultures differentiating into progeny consisting predominantly of cholinergic neurons could be readily transfected with expression vectors using liposomes and expressed beta-gal without significant morphologic changes of the differentiated neurons. The systems should be useful for the study of promoters and various expressed proteins, including those involved in axonal transport.
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PMID:Activity assays of nine heterogeneous promoters in neural and other cultured cells. 806 55

The kinetics of amyloid fibril formation by beta-amyloid peptide (Abeta) are typical of a nucleation-dependent polymerization mechanism. This type of mechanism suggests that the study of the interaction of Abeta with itself can provide some valuable insights into Alzheimer disease amyloidosis. Interaction of Abeta with itself was explored with the yeast two-hybrid system. Fusion proteins were created by linking the Abeta fragment to a LexA DNA-binding domain (bait) and also to a B42 transactivation domain (prey). Protein-protein interactions were measured by expression of these fusion proteins in Saccharomyces cerevisiae harboring lacZ (beta-galactosidase) and LEU2 (leucine utilization) genes under the control of LexA-dependent operators. This approach suggests that the Abeta molecule is capable of interacting with itself in vivo in the yeast cell nucleus. LexA protein fused to the Drosophila protein bicoid (LexA-bicoid) failed to interact with the B42 fragment fused to Abeta, indicating that the observed Abeta-Abeta interaction was specific. Specificity was further shown by the finding that no significant interaction was observed in yeast expressing LexA-Abeta bait when the B42 transactivation domain was fused to an Abeta fragment with Phe-Phe at residues 19 and 20 replaced by Thr-Thr (AbetaTT), a finding that is consistent with in vitro observations made by others. Moreover, when a peptide fragment bearing this substitution was mixed with native Abeta-(1-40), it inhibited formation of fibrils in vitro as examined by electron microscopy. The findings presented in this paper suggest that the two-hybrid system can be used to study the interaction of Abeta monomers and to define the peptide sequences that may be important in nucleation-dependent aggregation.
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PMID:Two-hybrid system as a model to study the interaction of beta-amyloid peptide monomers. 870 Aug 86

A fusion protein between beta-galactosidase and the amino-terminal domain of amyloid precursor protein (APP) was used as an immunogen for the production of monoclonal antibodies. One of these antibodies, the 5D12 monoclonal antibody, labeled the neurofibrillary tangles (NFT) by immunohistochemistry, as well as isolated paired helical filaments (PHF) in electron microscopy. In immunoassay, the ascitic fluid produced by the 5D12 clone was demonstrated to contain a high titer of antibodies to heat-stable microtubule associated proteins (MAPs). By immunoblotting, the proteins recognized in heat-stable MAPs were found to correspond to tau proteins. The 5D12 antibody recognized normal tau isolated from rat and human brain homogenates, and PHF-tau isolated from the brain of patients with Alzheimer's disease (AD). By immunoblotting, the 5D12 antibody also recognized the full-length recombinant tau protein but not the fusion protein used as an immunogen. The immunoreactivity of the 5D12 antibody with tau was completely abolished when the half-carboxy domain of tau, containing the tubulin-binding repeats, was removed. This study demonstrates that the use of the amino-terminal domain of APP as an immunogen led to the generation of a monoclonal antibody to the half-carboxy domain of tau.
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PMID:Generation of a monoclonal antibody to the carboxy-terminal domain of tau by immunization with the amino-terminal domain of the amyloid precursor protein. 897 5

In an attempt to elucidate the pathological implications of intracellular accumulation of the amyloid precursor protein (APP) in postmitotic neurons in vivo, we transferred APP695 cDNA into rat hippocampal neurons by using a replication-defective adenovirus vector. We first improved the efficiency of adenovirus-mediated gene transfer into neurons in vivo by using hypertonic mannitol. When a beta-galactosidase-expressing recombinant adenovirus suspended in 1 M mannitol was injected into a dorsal hippocampal region, a number of neurons in remote areas were positively stained, presumably owing to increased retrograde transport of the virus. When an APP695-expressing adenovirus was injected into the same site, part of the infected neurons in the hippocampal formation underwent severe degeneration in a few days, whereas astrocytes near the injection site showed no apparent degeneration. These degenerating neurons accumulated different epitopes of APP, and beta/A4 protein (Abeta)-immunoreactive materials were undetected in the extracellular space. A small number of degenerating neurons showed nuclear DNA fragmentation. Electron microscopic examinations demonstrated that degenerating neurons had shrunken perikarya along with synaptic abnormalities. Microglial cells/macrophages were often found in close proximity to degenerating neurons, and in some cases they phagocytosed these neurons. These results suggest that intracellular accumulation of wild-type APP695 causes a specific type of neuronal degeneration in vivo in the absence of extracellular Abeta deposition.
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PMID:Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer. 950

Nerve growth factor therapy has been proposed as a potential means of preventing degeneration of basal forebrain cholinergic neurons in Alzheimer's disease and thereby improving cognition. However, NGF has been reported to upregulate expression of the beta-amyloid precursor protein, which in turn could accelerate deposition of "mature" beta-amyloid in the brain. To address this possibility, the brains of 16 adult and aged rhesus monkeys were examined for beta-amyloid plaque deposition in the presence or absence of NGF treatment. Six aged monkeys received intraparenchymal grafts into the cholinergic basal forebrain of autologous cells genetically modified to secrete NGF, six aged monkeys received intraparenchymal grafts of autologous control cells expressing the reporter gene beta-galactosidase, and four adult nonoperated monkeys served as additional controls. All brains were examined for expression of mature beta-amyloid using an antibody recognizing amino acids 1-40 of the beta-amyloid peptide. Amyloid plaques were systematically quantified in representative sections of the temporal, frontal, cingulate, insular, and parietal cortices and in the amygdala and hippocampus. Results disclosed that aging resulted in an increase in amyloid plaque formation: no plaques at all were detected in nonaged monkeys, whereas a mean of 20 +/- 13 plaques per section were present in control-aged monkeys. Aged subjects with intraparenchymal NGF-secreting grafts for 3 months contained a mean of 29 +/- 14 plaques per section, an amount that did not differ significantly from control-aged monkeys (P = 0.66). Thus, 3 months of intraparenchymal NGF delivery did not significantly increase beta-amyloid deposition.
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PMID:Targeted intraparenchymal delivery of human NGF by gene transfer to the primate basal forebrain for 3 months does not accelerate beta-amyloid plaque deposition. 987 92

Forced overexpression of wild-type Alzheimer amyloid precursor protein (APP) causes postmitotic neurons to degenerate. Caspase-3 (CPP32) is a principal cell death protease involved in neuronal apoptosis during physiological development and under pathological conditions. Here, we investigated whether APP overexpression activates caspase-3 in human postmitotic neurons using adenovirus-mediated gene transfer. When a recombinant adenovirus vector expressing human wild-type APP695 was infected in vitro into neurally differentiated embryonal carcinoma NT2 cells, only postmitotic neurons underwent severe degeneration. Before neurodegeneration, full-length APP- and Abeta-immunoreactive peptides were accumulated in infected neurons, and caspase-3-like protease activity was markedly elevated. Western blot analysis revealed that activated caspase-3 subunits were generated in APP-accumulating neurons. Such neuronal caspase-3 activation was undetectable in NT2 neurons infected with beta-galactosidase-expressing adenovirus. Addition of the caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde to the culture medium significantly reduced the severity of degeneration exhibited by APP-overexpressing neurons. Immunocytochemical analyses revealed that some APP-accumulating neurons contained activated caspase-3 subunits and exhibited the characteristics of apoptosis, such as chromatin condensation and DNA fragmentation. Activation of caspase-3 was also observed in vivo in rat hippocampal neurons infected with the APP-expressing adenovirus. These results suggest that wild-type APP is an intrinsic activator of caspase-3-mediated death machinery in postmitotic neurons.
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PMID:Activation of neuronal caspase-3 by intracellular accumulation of wild-type Alzheimer amyloid precursor protein. 1043 52

Transgenic mouse lines were generated that expressed a 2-kb amyloid precursor protein (APP) promoter/beta-galactosidase reporter gene construction. In brain, hippocampal pyramidal neurons, neurons in the deeper layers of cerebral cortex, and neurons in several thalamic nuclei were heavily labeled by beta-galactosidase histochemistry. In general, molecular layers and white matter regions did not express the reporter gene. When compared with in situ hybridization for endogenous murine APP RNA, the striatum and outer layers of cerebral cortex had little reporter expression. Thus, the match between reporter expression and endogenous APP expression in brain was not perfect. A similar mismatch between the relative expression of the reporter gene and endogenous APP RNA distribution was found in homogenates from several organs. Although prior work in transgenic mice found similar mismatches in reporter gene distribution, none had tested the APP promoter construct in response to neuronal injury. Kainic acid injections successfully increased murine APP expression in the transgenic mice, but had no effect on the reporter gene expression. Based on these data and those collected by others, we conclude that the 2-kb region upstream of the APP transcription initiation site contains some elements responsible for the tissue-specific expression of this gene, but does not contain all the cis-acting elements sufficient for either the differential tissue distribution of this gene or the regulation of this gene subsequent to neural damage.
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PMID:Mice transgenic for a human amyloid precursor protein promoter-lacZ reporter construct. 1069 Dec 98

The physiological role of amyloid precursor protein (APP), whose anomalous metabolite is a putative pathogen for Alzheimer disease, remains unclear. From the enhanced responsiveness to glutamate in cultured hippocampal neurons after the introduction of cDNA of APP695 (an isoform of APP dominant in human brain) using an adenovirus vector, we have recently raised the hypothesis that APP modulates neuronal sensitivity to glutamate. To test this hypothesis, we utilized here the unique effects of glutamate on the survival of different types of neurons. It is known that hippocampal neurons undergo deterioration in 24 h after application of glutamate in a dose-dependent manner. This vulnerability was increased in the cells transfected with adenovirus carrying cDNA of APP695. By contrast, it is known that cerebellar granule neurons require for their survival the supplementation of NMDA to the medium. The dose of NMDA required for survival was reduced after the transfection of the APP-adenovirus to cerebellar granule neurons. These enhancing effects of APP on the glutamate-induced vulnerability in hippocampal neurons and the glutamate (NMDA)-dependent survival in cerebellar neurons were blocked by glutamate receptor inhibitors, and were not seen after application of a control adenovirus carrying cDNA of beta-galactosidase. Since the effects of glutamate were enhanced in both directions, the hypothesis became more likely that one of the physiological functions of cellular APP is the regulation of glutamate receptors.
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PMID:Neurotoxic and neuroprotective effects of glutamate are enhanced by introduction of amyloid precursor protein cDNA. 1168 50


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