Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PHOSPHOPYRUVIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2003

Tissue inhibitor of metalloproteinases-3 and matrix metalloproteinase-3 regulate neuronal sensitivity to doxorubicin-induced apoptosis.

Metalloproteinase activity at the cell surface influences cellular sensitivity to extrinsic death vs. survival signals in a variety of cell types, through proteolytic shedding of cell surface signalling molecules. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a unique natural metalloproteinase inhibitor that plays a pro-apoptotic role through its ability to inhibit metalloproteinases that proteolytically cleave death receptors and their ligands from the cell surface. To study the convergence of metalloproteinase activity and death receptor signalling in neurons, we established an in vitro model of neuronal apoptosis utilizing the chemotherapeutic drug, doxorubicin (Dox). Primary cultures established from embryonic rat cerebral cortices displayed robust and selective neuronal apoptosis in response to Dox, an effect that was dependent on the activation of the death receptor, Fas. We demonstrate that both TIMP-3 and matrix metalloproteinase-3 (MMP-3) are constitutively expressed by primary cortical neurons in culture, and selectively modulated Fas-mediated neuronal apoptosis induced by Dox. Metalloproteinase inhibition by TIMP-3 was found to be necessary for Dox-induced neuronal death, whereas addition of active MMP-3 markedly attenuated apoptosis and diminished Fas-Fas ligand interaction at the cell surface. These observations implicate a physiological role for the balance of TIMP-3 and MMP-3 activity at the neuronal surface in regulating death receptor sensitivity. The convergence of metalloproteinase activity and death receptor signalling at the cell surface may influence neuronal cell death vs. survival decisions.

Animals↗
PubMed2001

Lateral transfer at the gene and subgenic levels in the evolution of eukaryotic enolase.

Enolase genes from land plants and apicomplexa (intracellular parasites, including the malarial parasite, Plasmodium) share two short insertions. This observation has led to the suggestion that the apicomplexan enolase is the product of a lateral transfer event involving the algal endosymbiont from which the apicomplexan plastid is derived. We have examined enolases from a wide variety of algae, as well as ciliates (close relatives of apicomplexa), to determine whether lateral transfer can account for the origin of the apicomplexan enolase. We find that lateral gene transfer, likely occurring intracellularly between endosymbiont and host nucleus, does account for the evolution of cryptomonad and chlorarachniophyte algal enolases but fails to explain the apicomplexan enolase. This failure is because the phylogenetic distribution of the insertions--which we find in apicomplexa, ciliates, land plants, and charophyte green algae--directly conflicts with the phylogeny of the gene itself. Protein insertions have traditionally been treated as reliable markers of evolutionary events; however, these enolase insertions do not seem to reflect accurately the evolutionary history of the molecule. The lack of congruence between insertions and phylogeny could be because of the parallel loss of both insertions in two or more lineages, or what is more likely, because the insertions were transmitted between distantly related genes by lateral transfer and fine-scale recombination, resulting in a mosaic gene. This latter process would be difficult to detect without such insertions to act as markers, and such mosaic genes could blur the "tree of life" beyond the extent to which whole-gene lateral transfer is already known to confound evolutionary reconstruction.

Amino Acid Sequence↗
PubMed2005

ATP production in Chlamydomonas reinhardtii flagella by glycolytic enzymes.

Eukaryotic cilia and flagella are long, thin organelles, and diffusion from the cytoplasm may not be able to support the high ATP concentrations needed for dynein motor activity. We discovered enzyme activities in the Chlamydomonas reinhardtii flagellum that catalyze three steps of the lower half of glycolysis (phosphoglycerate mutase, enolase, and pyruvate kinase). These enzymes can generate one ATP molecule for every substrate molecule consumed. Flagellar fractionation shows that enolase is at least partially associated with the axoneme, whereas phosphoglycerate mutase and pyruvate kinase primarily reside in the detergent-soluble (membrane + matrix) compartments. We further show that axonemal enolase is a subunit of the CPC1 central pair complex and that reduced flagellar enolase levels in the cpc1 mutant correlate with the reduced flagellar ATP concentrations and reduced in vivo beat frequencies reported previously in the cpc1 strain. We conclude that in situ ATP synthesis throughout the flagellar compartment is essential for normal flagellar motility.

Adenosine Triphosphate↗
PubMed1997

Verocay body--prominent cutaneous schwannoma.

We report on eight cases of a distinct variant of cutaneous schwannoma characterized by prominent Verocay body formation (75-100% of the tumor bulk) that may cause considerable diagnostic difficulties. Like ordinary cutaneous schwannomas, these lesions preferred the head and neck region of young adults without sexual predilection and were clinically interpreted as cyst, basal cell carcinoma, or nevus. Histological examination revealed well-circumscribed nodules. Three of them consisted exclusively of nodular or ribbon-like Verocay bodies. A variable admixture of Antoni A or B type of differentiation (< 25%) was seen in five other cases. The following patterns were seen: fascicular spindle-shaped, onion-like epithelioid, myxoid-hypocellular, and degenerated ("ancient") with prominent fibrosis/hyalinosis and occasional bizarre giant cells. Immunohistochemically, the lesions were positive for S-100 protein (and vimentin) but negative for a broad panel of neurogenic and intermediate filament markers. The capsule showed focal labeling for EMA and--when it was markedly thickened--also for SMA. Labeling with E9, an anti-metallothionein marker indicative of cell activity, was negative, underscoring the slow growth potential of these lesions. No recurrence was seen in the six patients with follow-up information. The differential diagnosis includes other lesions with prominent palisading. (Amianthoid) myofibroblastoma and palisading leiomyoma are consistently positive for SMA and desmin, respectively. Palisading cutaneous fibrous histiocytoma and myofibroblastic dermatofibroma are variably positive for Factor XIIIa, SMA, and E9 and/or NK1C3 (CD57). Palisaded encapsulated neuromas are primarilly differentiated by the presence of nerve fibers with myelin sheaths.

Adolescent↗
PubMed1993

HU-211, a non-psychotropic cannabinoid, rescues cortical neurones from excitatory amino acid toxicity in culture.

The present study examined potential neuroprotective effects of HU-211, a synthetic non-psychotropic cannabinoid with non-competitive NMDA antagonist properties on neurones exposed to various excitotoxins in culture. HU-211 was found to protect neurones from NMDA and quisqualate-induced toxicity but not that produced by AMPA or kainate. NMDA-mediated neurotoxicity was blocked by HU-211 in a dose dependent manner with an EC50 = 3.8 +/- 0.9 microM. Radioligand binding studies have shown that HU-211 inhibits the binding of [3H]MK-801 to rat forebrain membranes (KI = 11.0 microM +/- 1.323) in a competitive manner, but was unable to displace [3H]kainate and [3H]AMPA binding. These data suggest that the neuroprotective activity of HU-211 is directly associated with the NMDA receptor channel and possibly with the quisqualate receptor of the metabotropic class. Thus, HU-211 appears to act as an NMDA open channel blocker and shows promise as a novel neuroprotectant for clinical use.

Amino Acids↗
PubMed2000

Correlation between N-acetylaspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion.

The aim of the present study was to evaluate the use of the endogenous neuronal compound N-acetylaspartate (NAA) as a marker of neuronal damage after focal cerebral ischemia in mice. After occlusion of the middle cerebral artery (MCAO) the ischemic cortex was sampled, guided by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and the NAA concentration was measured by high-pressure liquid chromatography (HPLC). Conventional histology and immunohistological methods using antibodies against neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, glial fibrillary acidic protein (GFAP), and carbodiamide-linked NAA and N-acetylaspartylglutamate (NAAG). The level of NAA rapidly declined to 50% and 20% of control levels in infarcted tissue after 6 hours and 24 hours, respectively. No further decrease was observed during the observation period of 1 week. Within the first 6 hours the number of normal-appearing neurons in the infarcted cortical tissue decreased to 70% of control, of which the majority were eosinophilic. After 24 hours almost no normal-appearing neurons were seen. The number of eosinophilic neurons decreased steadily to virtually zero after 7 days. The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages. This granulomatous material also stained positive for NAA. The number of cells with positive GFAP immunoreactions progressively increased in the circumference of the infarct. They also showed increased immunoreaction against NAA and NSE. The study shows that the level of NAA 7 days after ischemia does not decline to zero but remains at 10% to 20% of control values. The fact NAA is trapped in cell debris and NAA immunoreactivity is observed in the peri-infarct areas restricts its use as a marker of neuronal density.

Animals↗
PubMed1987

An immunohistochemical study of the enteric neural plexi in Hirschsprung's disease.

The diagnosis of Hirschsprung's disease relies upon histology and acetylcholinesterase histochemistry of the enteric neural plexi. A distinctive neurofilament protein staining pattern has been claimed in Hirschsprung's disease. We studied 10 colons affected by Hirschsprung's disease, together with appropriate controls using antibodies to neurofilament protein (NFP; monoclonal), neurone-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S-100 protein (all polyclonal), and conventional histology and histochemistry, seeking an immunohistochemical diagnostic method. We found staining for NFP, NSE and S-100 protein of many of the nerve fibres and satellite cells in the enteric plexi, but without significant differences between affected and unaffected colons. Staining for GFAP was weakly positive in a minority of cases and controls and the majority of neurones in control sections stained for NSE. In contrast to acetylcholinesterase little staining was localized in the lamina propria. Staining for NSE and S-100 is useful in identifying immature ganglion cells in paediatric large intestine.

Acetylcholinesterase↗
PubMed2005

Supratentorial primitive neuroectodermal tumours of the brain: multidirectional differentiation does not influence prognosis. A clinicopathological report of 18 patients.

AIMS: To examine the clinical and pathological characteristics of supratentorial primitive neuroectodermal tumours (PNETs) in a retrospective series of 18 patients, according to the strict definition of the World Health Organization classification of tumours that excludes other types of malignant embryonal tumours of the brain. METHODS AND RESULTS: Eleven children and seven adults with supratentorial PNETs were diagnosed between 1993 and 2002 and their medical records were reviewed. An immunohistochemical study was performed on formalin-fixed paraffin-embedded tissue of 18 primary tumours and five recurrences with antibodies for neuronal (neuron specific enolase, synaptophysin, neurofilament, chromogranin A), epithelial [epithelial membrane antigen (EMA), cytokeratin], glial [glial fibrillary acidic protein (GFAP)], muscle (desmin, h-caldesmon, alpha-smooth muscle actin, myogenin) differentiation and with two anti-CD99 antibodies. All tumours showed at least one neuronal marker except chromogranin A; a variable number of cells were GFAP+ or EMA+ in 18/23 tumours. Six primary tumours and one recurrence were positive for cytokeratin and/or one muscle antigen except myogenin. CD99 was observed in 33% of the cases. The mean duration of overall survival was 20 months. The estimated overall survival rates were 61% at 1 year, 29% at 2 years, and 18% at 3 years. Two factors of poor prognosis were identified by univariate analysis: a positive cerebrospinal fluid cytology at diagnosis and the absence of complete resection. No distinct immunophenotype was statistically related to survival. CONCLUSIONS: A multidirectional differentiation is a frequent event in supratentorial PNETs but has no apparent influence on the outcome of this aggressive neoplasm.

12E7 Antigen↗
PubMed2004

Quantitative effects produced by modifications of neuronal activity on the size of GABAA receptor clusters in hippocampal slice cultures.

The number and strength of GABAergic synapses needs to be precisely adjusted for adequate control of excitatory activity. We investigated to what extent the size of GABA(A) receptor clusters at inhibitory synapses is under the regulation of neuronal activity. Slices from P7 rat hippocampus were cultured for 13 days in the presence of bicuculline or 4-aminopyridine (4-AP) to increase neuronal activity, or DNQX to decrease activity. The changes provoked by these treatments on clusters immunoreactive for the alpha1 and alpha2 subunits of the GABA(A) receptor or gephyrin were quantitatively evaluated. While an increase in activity augmented the density of these clusters, a decrease in activity provoked, in contrast, a decrease in their density. An inverse regulation was observed for the size of individual clusters. Bicuculline and 4-AP decreased whilst DNQX increased the mean size of the clusters. When the pharmacological treatments were applied for 2 days instead of 2 weeks, no effects on the size of the clusters were observed. The variations in the mean size of individual clusters were mainly due to changes in the number of small clusters. Finally, a regulation of the size of GABA(A) receptor clusters occurred during development in vivo, with a decrease of the mean size of the clusters between P7 and P21. This physiological change was also the result of an increase in the number of small clusters. These results indicate that neuronal activity regulates the mean size of GABA(A) receptor- and gephyrin-immunoreactive clusters by modifying specifically the number of synapses with small clusters of receptors.

4-Aminopyridine↗
PubMed1997

Molecular characterization of the Entamoeba histolytica enolase gene and modelling of the predicted protein.

Entamoeba histolytica obtains its energy mainly from glucose fermentation. Enzymes involved in this pathway could be potential targets for antiparasite drugs. Here we report the molecular characterization of the E. histolytica enolase gene (Ehenl-I), which in a single copy is located on the 1.6 Mb chromosome. It is transcribed into a 1.4 kb mRNA which starts 13 nucleotides upstream of the ATG start codon. The sequence TATAAG, at -31, interacted with nuclear proteins suggesting that it has a TATA box function. Protein modelling allowed us to identify a putative specific region that differs from human enolase and could be a good target for the design of novel drugs against E. histolytica.

Amino Acid Sequence↗
PubMed1987

Transcription of the constitutively expressed yeast enolase gene ENO1 is mediated by positive and negative cis-acting regulatory sequences.

There are two enolase genes, ENO1 and ENO2, per haploid yeast genome. Expression of the ENO1 gene is quantitatively similar in cells grown on glucose or gluconeogenic carbon sources. In contrast, ENO2 expression is induced more than 20-fold in cells grown on glucose as the carbon source. cis-Acting regulatory sequences were mapped within the 5'-flanking region of the constitutively expressed yeast enolase gene ENO1. A complex positive regulatory region was located 445 base pairs (bp) upstream from the transcriptional initiation site which was required for ENO1 expression in cells grown on glycolytic or gluconeogenic carbon sources. A negative regulatory region was located 160 bp upstream from the transcriptional initiation site. Sequences required for the function of this negative regulatory element were mapped to a 38-bp region. Deletion of all or a portion of these latter sequences permitted glucose-dependent induction of ENO1 expression that was quantitatively similar to that of the glucose-inducible ENO2 gene. The negative regulatory element therefore prevents glucose-dependent induction of the ENO1 gene. Hybrid 5'-flanking regions were constructed which contained the upstream regulatory sequences of one enolase gene fused at a site upstream from the TATAAA box in the other enolase gene. Analysis of the expression of enolase genes containing these hybrid 5'-flanking region showed that the positive regulatory regions of ENO1 and ENO2 were functionally similar, as were the regions extending from the TATAAA boxes to the initiation codons. Based on these studies, we conclude that the negative regulatory element plays the critical role in maintaining the constitutive expression of the ENO1 structural gene in cells grown on glucose or gluconeogenic carbon sources.

Amino Acid Sequence↗
PubMed1995

Weak acid effects and fluoride inhibition of glycolysis by Streptococcus mutans GS-5.

Fluoride and a variety of other weak acids acted to reduce reversibily the acid tolerance of glycolysis by intact cells of Streptococcus mutans GS-5 as shown by higher final pH values in acid-drop experiments with glucose in excess. The order of effectiveness was fluoride > indomethacin > ibuprofen > ketoprofen > salicylate > sorbate > cinnamate > p-hydroxybenzoate > benzoate > ascorbate. Only fluoride also acted as an inhibitor of the glycolytic enzyme enolase. However, enolase in permeabilized cells was also inhibited by acidification with a sharp drop-off in activity between pH 6 and 5. It was proposed that the weak acids, including fluoride, acted to reduce glycolytic acid tolerance by enhancing cytoplasmic acidification and thereby inhibiting enzymes such as enolase. The potencies of the acids could not be predicted accurately from knowledge of pKa values, octanol-water partition coefficients, and molecular weights. It was concluded that their modes of action in acid sensitization involved perturbations of membrane function in addition to their acting as transmembrane carriers of protons. Methylparaben (methyl ester of p-hydroxybenzoate) was also a sensitizer but was less effective than the parent acid.

Acids↗
PubMed1992

Tissue markers in the diagnosis and prognosis of prostatic carcinoma.

Prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and beta-microseminoprotein are organ-specific markers. Also Leu-7 may be regarded as an organ-specific marker. The main utilization of PAP and PSA immunostaining is to establish the prostatic origin of a carcinoma. Changes of PAP and PSA immunoreactivity may be correlated with histologic grade of prostatic carcinoma. Keratin expression assessment is useful to identify prostatic basal cells or epithelial secretory cells. Neuroendocrine marker reactivity in prostatic carcinoma seems to be related with increasing histologic grade and tumor progression.

Acid Phosphatase↗
PubMed2003

Matrix cells from Wharton's jelly form neurons and glia.

We have identified an easily attainable source of primitive, potentially multipotent stem cells from Wharton's jelly, the matrix of umbilical cord. Wharton's jelly cells have been propagated in culture for more than 80 population doublings. Several markers for stem cells, including c-kit (CD117), and telomerase activity are expressed in these cells. Treatment with basic fibroblast growth factor overnight and low-serum media plus butylated hydroxyanisole and dimethylsulfoxide induced Wharton's jelly cells to express a neural phenotype. Within several hours of this treatment, Wharton's jelly cells developed rounded cell bodies with multiple neurite-like extensions, similar to the morphology of neural stem cells. Neuron-specific enolase (NSE), a neural stem cell marker, was expressed in these cells, as shown by immunocytochemistry. Immunoblot analysis showed similar levels of NSE expression in both untreated and induced Wharton's jelly cells. After 3 days, the induced Wharton's jelly cells resembled bipolar or multipolar neurons, with processes that formed networks reminiscent of primary cultures of neurons. The neuron-like cells in these cultures stained positively for several neuronal proteins, including neuron-specific class III beta-tubulin, neurofilament M, an axonal growth-cone-associated protein, and tyrosine hydroxylase. Immunoblot analysis showed increasing levels of protein markers for mature neurons over time post induction. Markers for oligodendrocytes and astrocytes were also detected in Wharton's jelly cells. These exciting findings show that cells from the matrix of umbilical cord have properties of stem cells and may, thus, be a rich source of primitive cells. This study shows their capacity to differentiate into a neural phenotype in vitro.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMedDate not supplied

Primitive neuroectodermal tumors: ultrastructural and immunohistochemical studies.

We report here ultrastructural and immunohistochemical studies of neuroblastic differentiation in the retrospective (n = 17) and prospective (n = 26) series of primitive neuroectodermal tumors (PNETs). By electron microscopy, neuritelike structures containing parallel-oriented microtubules, adhesive plaque junctions, and pleomorphic dense-core vesicles were found in the majority of tumor specimens while synaptic specializations were very rare. By immunohistochemistry, synaptophysin appeared to be the most reliable marker for neuroblastic differentiation present in the most reliable marker for neuroblastic differentiation present in the majority of tumors, while 200 kDa neurofilament protein was immunovisualized in a lower proportion of tumors. Glial fibrillary acidic protein (GFAP) was expressed in both reactive astrocytes and in a small proportion of otherwise typical neoplastic cells. We conclude that the majority of PNETs revealed diverse differentiation and that electron microscopy is still the most reliable tool for its detection followed by immunohistochemistry for synaptophysin.

Adolescent↗