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PubMedDate not supplied

Prostaglandin G/H synthase-2 (cyclooxygenase-2) mRNA expression is decreased in Alzheimer's disease.

Recent evidence suggests that the use of nonsteroidal anti-inflammatory drugs (NSAIDS) is beneficial for therapy or prevention of Alzheimer's disease (AD). The major anti-inflammatory action of NSAIDS is to inhibit prostaglandin G/H synthase-2 (PGHS-2), the first committed enzymatic step for prostaglandin biosynthesis. We have previously shown that PGHS-2 message is induced by Interleukin-1 beta and other inflammatory mediators in primary cultures of rodent astrocytes. To determine whether similar elevations of PGHS-2 occur as part of the gliosis in AD, we quantified PGHS-2 mRNA levels in control and AD brain by Northern hybridization analysis. To our surprise we found that PGHS-2 mRNA levels were reduced threefold in AD neocortex relative to control brain tissue. In contrast, levels were not reduced in putamen, an area that is relatively spared in AD. To localize PGHS-2 mRNA production in control and AD brain, sections of neocortex and hippocampus were hybridized with a 35S-labeled riboprobe for human PGHS-2 followed by immunocytochemistry with antibodies against neuron specific enolase (NSE) or glial fibrillary acidic protein (GFAP). Our findings indicate that PGHS-2 message is primarily localized to cells that stain for NSE rather than GFAP. Furthermore, in the three cases we examined, PGHS-2 hybridization per neuron appeared to be reduced in AD. Thus, the decrease we observe in overall PGSH-2 mRNA levels is likely to reflect both the known decline in numbers of neurons in AD as well as a lowered capacity for neuronal synthesis of PGHS-2, perhaps due to dysfunction or a loss of synaptic input.

Aged↗
PubMed1987

Localization of neuron-specific enolase (NSE) mRNA in human brain.

In situ hybridization with biotinylated DNA and RNA probes derived from the 3' untranslated region of human neuron-specific or gamma gamma-enolase (NSE) permits histochemical detection of NSE mRNA in autopsy samples of human brain. In both aged controls and Alzheimer's disease (AD) patients, NSE probe hybridized with variable intensity to nerve cells in visual cortex and cerebellum, but not to glial or liver cells. These results provide evidence that NSE mRNA is expressed in neurons in human brain tissue, pattern of NSE mRNA expression in unaffected brain regions in AD is qualitatively normal, and NSE mRNA expression may vary widely among different classes of neurons.

Adult↗
PubMed2004

Chromosomal imbalances in sporadic neuroendocrine tumours of the thymus.

Neuroendocrine (carcinoid) tumours of the thymus are rare neoplasms characterized by a highly malignant clinical behavior. Some of these tumors are associated with MEN1. In this study we evaluated 10 cases of sporadic thymic neuroendocrine tumours using immunohistochemistry and comparative genomic hybridization (CGH). All tumours showed a diffuse expression of neuron specific enolase (NSE) and synaptophysin. Chromosomal imbalances were detected in 8/10 cases, the most frequent gains were seen on chromosome Xp (3/10 cases), 7p, 7q, 11q, 12q, and 20q (2/10 each), losses were most frequently detected at 6q (5/10 each), 6p (3/10 each), 4q (3/10 each), 3p, 10q, 11q and 13 q (2/10 each). These CGH data show a degree of overlap with chromosomal imbalances commonly observed in advanced thymomas.

Adult↗
PubMed2004

Plasmin(ogen)-binding alpha-enolase from Streptococcus pneumoniae: crystal structure and evaluation of plasmin(ogen)-binding sites.

Alpha-enolases are ubiquitous cytoplasmic, glycolytic enzymes. In pathogenic bacteria, alpha-enolase doubles as a surface-displayed plasmin(ogen)-binder supporting virulence. The plasmin(ogen)-binding site was initially traced to the two C-terminal lysine residues. More recently, an internal nine-amino acid motif comprising residues 248 to 256 was identified with this function. We report the crystal structure of alpha-enolase from Streptococcus pneumoniae at 2.0A resolution, the first structure both of a plasminogen-binding and of an octameric alpha-enolase. While the dimer is structurally similar to other alpha-enolases, the octamer places the C-terminal lysine residues in an inaccessible, inter-dimer groove restricting the C-terminal lysine residues to a role in folding and oligomerization. The nine residue plasminogen-binding motif, by contrast, is exposed on the octamer surface revealing this as the primary site of interaction between alpha-enolase and plasminogen.

Aspartic Acid↗
PubMed1986

Isolation of murine neuron-specific and non-neuronal enolase cDNA clones.

cDNA clones corresponding to subunits of neuron-specific (gamma gamma and alpha gamma) and non-neuronal (alpha alpha) enolase isozymes were characterized from two mouse brain cDNA libraries. Our hybridization data revealed a partial homology of the coding sequences of mouse alpha, mouse gamma and rat gamma mRNAs. The noncoding sequences, however, appear to be specific for each mouse mRNA. Although coding for two polypeptides of the same molecular weight, the mRNA for the gamma subunit (2600 bases) is larger than that for the alpha subunit (1900 bases). The noncoding sequences for neuron-specific gamma mRNA (about 1300 bases) are therefore longer than those of the non-nervous tissue specific alpha mRNA (about 600 bases).

Animals↗
PubMed1981

Binding of terbium (III) to yeast enolase.

Several independent criteria indicate 2 mol of terbium (III) bind to yeast enolase in the absence of substrate-fluorescence titrations of enzyme and metal, effects on thermal stability and published ultrafiltration and inhibition experiments. These measurements also suggest the terbium binding sites are the same as those normally occupied by "conformational" magnesium. Terbium binds much more strongly than magnesium, however, and measurements of the kinetics of the absorbance change in the terbium-enzyme on adding excess EDTA suggest the terbium-enzyme dissociation constant is about 1/500 that of the magnesium-enzyme. Measurements of enzyme activity as a function of substrate concentration show that terbium permits no enzymatic activity. However, magnesium competes more effectively with the lanthanide if the substrate analogue 3-aminoenolpyruvate 2-phosphate (AEP) is present. The fluorescence of the lanthanide is not readily observed on exciting the terbium-enzyme at 280 nm, indicating the absence of tyrosines or tryptophans in the coordination sphere of the metal. Excitation of terbium using 488 nm radiation from an argon ion laser shows the fluorescence of the metal is enhanced by binding to the enzyme. EDTA and carbonate have similar effects. This suggests carboxyl groups are involved in binding metal at the conformational sites of yeast enolase. Measurements of lifetimes of enzyme-bound terbium in the presence and absence of D2O indicated three moles of water remained on each of the bound metals, independently of the buffer used. If enzyme-bound terbium is assumed to be nine-coordinate, the metal must bind to six groups from the enzyme. The presence of substrate does not markedly affect the emission spectrum of the bound terbium or the number of water molecules remaining on the metal, but calorimetric measurements show that substrate binds to the terbium enzyme.

Binding Sites↗
PubMed2003

Identification of genes that are induced after cadmium exposure by suppression subtractive hybridization.

The heavy metal cadmium is a xenobiotic toxicant of environmental and occupational concern and it has been classified as a human carcinogen. Inhalation of cadmium has been implicated in the development of emphysema and pulmonary fibrosis, but, the detailed mechanism by which cadmium induces adverse biological effects is not yet known. Therefore, we undertook the investigation of genes that are induced after cadmium exposure to illustrate the mechanism of cadmium toxicity. For this purpose, we employed the polymerase chain reaction (PCR)-based suppression subtractive hybridization (SSH) technique. We identified 29 different cadmium-inducible genes in human peripheral blood mononuclear cells (PBMCs), such as macrophage migration inhibitory factor (MIF), lysophosphatidic acid acyltransferase-alpha, enolase-1alpha, VEGF, Bax, and neuron-derived orphan receptor-1 (Nor-1), which are known to be associated with inflammation, cell survival, and apoptosis. Induction of these genes by cadmium treatment was further confirmed by semi-quantitative reverse-transcription PCR. Further, we found that these genes were also induced after cadmium exposure in normal human lung fibroblast cell line, WI-38, suggesting potential use of this induction profile to monitor cadmium toxicity in the lung.

Acyltransferases↗
PubMed2004

Dendritic transport and localization of protein kinase Mzeta mRNA: implications for molecular memory consolidation.

Protein kinase Mzeta (PKMzeta) is an atypical protein kinase C isoform that has been implicated in the protein synthesis-dependent maintenance of long term potentiation and memory storage in the brain. Synapse-associated kinases are uniquely positioned to promote enduring consolidation of structural and functional modifications at the synapse, provided that kinase mRNA is available on site for local input-specific translation. We now report that the mRNA encoding PKMzeta is rapidly transported and specifically localized to synaptodendritic neuronal domains. Transport of PKMzeta mRNA is specified by two cis-acting dendritic targeting elements (Mzeta DTEs). Mzeta DTE1, located at the interface of the 5'-untranslated region and the open reading frame, directs somato-dendritic export of the mRNA. Mzeta DTE2, in contrast, is located in the 3'-untranslated region and is required for delivery of the mRNA to distal dendritic segments. Colocalization with translational repressor BC1 RNA in hippocampal dendrites suggests that PKMzeta mRNA may be subject to translational control in local domains. Dendritic localization of PKMzeta mRNA provides a molecular basis for the functional integration of synaptic signal transduction and translational control pathways.

Animals↗
PubMed2003

Primitive neuroectodermal tumor (PNET) of the urinary bladder.

We report on the clinical, morphologic, immunohistochemical, ultrastructural, and molecular cytogenetic features of a primitive neuroectodermal tumor (PNET) primarily arising in the urinary bladder. An 81-year-old man presented with lymphedema of the lower extremities, fatigue, and urge incontinence. Radiographically, a tumor filling the entire cavity of the urinary bladder and extending into the pelvic and retroperitoneal tissue was noted. Histology of tumor biopsies showed a highly cellular, focally necrotic small round-cell tumor with numerous mitoses and occasional rosette-like structures. The tumor cells displayed significant immunoreactivity for neuron-specific enolase (NSE) and the MIC2 gene product (CD99). Dense-core granules were detectable by electron microscopy. A molecular cytogenetic analysis using comparative genomic hybridization (CGH) revealed gains of the chromosomes 3p, 6, 8q, 12, 17q, and 21q. The patient died two weeks after diagnosis. To the best of our knowledge, this is the fifth reported case of a PNET of the urinary bladder, and the first that includes a molecular cytogenetic analysis based on CGH.

12E7 Antigen↗
PubMed1985

Molecular cloning and the nucleotide sequence of cDNA to mRNA for non-neuronal enolase (alpha alpha enolase) of rat brain and liver.

The nucleotide sequence for alpha alpha enolase (non-neuronal enolase: NNE) of rat brain and liver was determined from recombinant cDNA clones. The sequence was composed of 1722 bp which included the 1299 bp of the complete coding region, the 108 bp of the 5'-noncoding region and the 312 bp of the 3'-noncoding region containing a polyadenylation signal. In addition, the poly(A) tail was also found. A potential ribosome-binding site was located 30 nucleotides upstream to the initiation codon in the 5'-noncoding region. The amino acid sequence deduced from the nucleotide sequence was 433 amino acids in length and showed very high homology (82%) to the amino acid sequence of gamma gamma enolase (neuron-specific enolase: NSE), although the nucleotide sequence showed slightly lower homology (75%). The size of NNE mRNA was approximately 1800 bases by Northern transfer analysis and much shorter than that of NSE mRNA (2400 bases) indicating a short 3'-noncoding region. A dot-blot hybridization and Northern transfer analysis of cytoplasmic RNA from the developing rat brains using a labeled 3'-noncoding region of cDNA (no homology between NSE and NNE) showed a decrease of NNE mRNA at around 10 postnatal days and then a gradual increase to adult age without changes of mRNA size. Liver mRNA did not show any significant change during development.

Amino Acid Sequence↗
PubMed1986

Localization of cytomegalovirus proteins and genome during fulminant central nervous system infection in an AIDS patient.

Approximately one-half of autopsied acquired immune deficiency syndrome (AIDS) patients demonstrate probable human cytomegalovirus (CMV) infection of the central nervous system (CNS). Because CMV in brain tissue or cerebrospinal fluid is difficult to culture, we used antisera, and radioactive probes to diagnose CMV infection in the brain of an autopsied AIDS patient, who died of a fulminant CNS and systemic infection with CMV, suggesting a complete seeding of the ependymal regions possibly followed by a uniform ventriculofugal spread of the virus deep into the parenchyma. Cytomegalic cells were observed in optic nerve, retina, ependymal and subependymal regions of the brain and in the motor (but not sensory) root-CNS junctions. Immunocytochemistry demonstrated viral antigen predominantly in cytomegalic cells, which also stained positively for glial fibrillary acidic protein, S-100, or neuron-specific enolase, but not a common leukocyte antigen. Virions were visible in these cells examined by electron microscopy. No viral replication was observed in pineocytes, pituicytes or the choroid plexus. Morphologically normal cells that were CMV antigen-negative proved to be infected after in situ hybridization with well-defined human CMV DNA fragments. Hence, morphologically normal glia and neurons show restricted replication of CMV, indicating that such cells may be latently infected.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Neuron-specific enolase as a marker of in vitro neuronal damage. Part I: Assessment of neuron-specific enolase as a quantitative and specific marker of neuronal damage.

Enolase in cerebrospinal fluid is a sensitive marker for many types of neurological injuries including head injury and ischemia. We assessed neuron-specific enolase (NSE) as a quantitative and specific biochemical marker of neuronal damage in an experimental model of kainate neurotoxicity. Rat hippocampal cultures were treated with various concentrations of kainate. NSE release into the culture medium was compared with neuronal death estimated either by direct cell counting or by lactate dehydrogenase (LDH) release, largely used to quantify neuronal injury. A dose-response relationship was observed between kainate concentration and the amount of NSE released (r = -0.69; p < 0.05) as well as a significant correlation between NSE release and neuronal death (r = 0.64; p < 0.05). Likewise, a significant correlation was found between LDH and NSE release (r = 0.85; p < 0.05). The specificity of NSE as an indicator of neuronal death was demonstrated using immunocyto-chemistry labeling and measurement of NSE release by pure astrocyte cultures. We concluded that NSE is a reliable, quantitative, and specific marker of neuronal injury.

Animals↗
PubMed1993

Neuron-specific enolase as a marker of in vitro neuronal damage. Part II: Investigation of the astrocyte protective effect against kainate-induced neurotoxicity.

The protective effect of astrocytes on hippocampal neurons against kainate-induced toxicity was investigated using neuron-specific enolase as an indicator of neuronal death. Astrocyte-rich and astrocyte-poor mixed rat hippocampal cultures were submitted to various concentrations of kainate. At each kainate concentration, the amount of NSE released by neurons was significantly greater in astrocyte-poor than in astrocyte-rich cultures (p < 0.05). This protective effect was not observed when neuronal survival was tested on astrocyte-poor cultures in astrocyte-conditioned culture medium with or without 10(-4) M kainate. In conclusion, astrocytes significantly attenuate kainate toxicity on hippocampal neurons, and this effect is not mediated by a diffusible factor.

Animals↗
PubMed1988

Complete amino acid sequence of the neurone-specific gamma isozyme of enolase (NSE) from human brain and comparison with the non-neuronal alpha form (NNE).

The complete amino acid sequence (433 residues) of the human neurone-specific gamma isozyme of enolase (NSE) has been determined by a combination of direct amino acid sequencing and nucleotide sequencing of cloned cDNA. Substantial amino acid sequence of the non-neuronal alpha form of the enzyme was also obtained which agreed almost entirely with the indirect cDNA sequence. Comparison of the two human sequences shows no insertions or deletions, but 72 replacements. Comparison of the human gamma form with the corresponding isozyme from the rat shows only 7 replacements (compared to 27 changes between the human and rat alpha isozymes). We have identified regions of sequence difference between the human alpha and gamma forms that are mainly hydrophilic in character (residues 271-285, 298-316 and 416-433). These residues are on the surface of the three-dimensional structure and could be useful as immunogens to produce antibodies specific for the neurone-specific form.

Amino Acid Sequence↗
PubMed1993

Structural features of the human gene for muscle-specific enolase. Differential splicing in the 5'-untranslated sequence generates two forms of mRNA.

We report here the isolation and characterization of the human gene for the beta or muscle-specific isoform of the glycolytic enzyme enolase. The nucleotide sequence analysis revealed structural features, such as organization as 11 coding exons, the first exon consisting of an untranslated sequence and hence resembling sequences of the other two members of the gene family, the alpha and gamma enolase genes. The beta enolase locus spans about 6 kbp genomic DNA. Sequences matching the consensus sequence for muscle-specific regulatory factors are present in the 5'-flanking region and within the first intron. A combination of primer extension, S1 nuclease protection and RNA-sequencing experiments indicates that the gene has a unique transcriptional start site, 26 bp downstream of a TATA-like box; the differential usage of two donor sites within the untranslated exon I generates two alternatively spliced transcripts. The existence of the two mRNA, differing from one another in the presence or absence of a 42-nucleotide fragment in the leader sequence, was confirmed by cloning the corresponding cDNA using the rapid amplification of cDNA ends strategy. Secondary-structure predictions indicated that the leader sequences of the spliced forms could form hairpin structures with different free energies of formation, suggesting translational control.

Base Sequence↗
PubMed1992

Molecular characterization of the Zymomonas mobilis enolase (eno) gene.

The Zymomonas mobilis gene encoding enolase was cloned by genetic complementation of an Escherichia coli eno mutant. An enzyme assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the overexpression of enolase in E. coli clones carrying the Z. mobilis eno gene. The eno gene is present in a single copy of the Z. mobilis genome. Nucleotide sequence analysis of the eno region revealed an open reading frame of 1,293 bp that encodes a protein of 428 amino acids with a predicted molecular weight of 45,813. Comparison of the sequence of Z. mobilis enolase with primary amino acid sequences for other enolases indicates that the enzyme is highly conserved. Unlike all of the previously studied glycolytic genes from Z. mobilis that possess canonical ribosome binding sites, the eno gene is preceded by a modest Shine-Dalgarno sequence. The transcription initiation site was mapped by primer extension and found to be located within a 115-bp sequence that is 55.7% identical to a highly conserved consensus sequence found within the regulatory regions of highly expressed Z. mobilis genes. Northern RNA blot analysis revealed that eno is encoded on a 1.45-kb transcript. The half-life of the eno mRNA was determined to be 17.7 +/- 1.7 min, indicating that it is unusually stable. The abundance of the eno message is proposed to account for enolase being the most prevalent protein in Z. mobilis.

Amino Acid Sequence↗
PubMed1996

Molecular cloning of a genomic DNA for enolase from Aspergillus oryzae.

We have isolated an enolase gene (enoA) from Aspergillus oryzae by heterologous hybridization using the corresponding Saccharomyces cerevisiae ENO2 gene as a probe. A 2.9-kb BglII-fragment contained the entire structural gene enoA including 5'- and 3'- flanking regions. The homology between A. oryzae enoA and S. cerevisiae ENO2 genes is 66.9% when introns are removed. Genomic Southern analysis indicated that there is only one enolase gene in A. oryzae.

Amino Acid Sequence↗