Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aluminium salt was injected intracerebrally into rabbits resulting in experimental neurofibrillary change (ENFC) formation as a model of Alzheimer neurofibrillary change. Cathepsin D was purified from the experimental and the control rabbit brains and the enzymatic properties were further investigated. The specific activity of cathepsin D in the tissue homogenate from the ENFC brains was 27% higher than that of the control, reflecting the induction of the enzyme by aluminium injection. The apparent Km values of the control and ENFC enzymes were calculated to be 26.3 microM, 29.3 microM, respectively, when assayed with bovine hemoglobin as substrate. The heat inactivation proceeded linearly with time for the control enzyme but biphasically for the ENFC enzyme, suggesting that less-reactive type of cathepsin D was induced by aluminium injection. Other properties such as molecular weight, optimum pH and amino acid composition were similar to each other.
Biochem Mol Biol Int 1994 Apr
PMID:Enzymatic characterization of cathepsin D in rabbit brains with experimental neurofibrillary changes. 806 19

The Na+,K(+)-ATPase is an important enzyme in determining the ionic milieu of the cerebromicrovasculature and neurons. The effect of hypertension or aging on this enzyme, as well as its susceptibility to regulation by fatty acids or aluminum, is the focus of this study. A significant increase (34%) in the apparent affinity constant (KD) but no change in the maximum binding capacity (Bmax) for [3H]ouabain binding to the cerebromicrovascular Na+,K(+)-ATPase occurs after induction of acute hypertension. In addition, long chain unsaturated fatty acids stimulate the binding of [3H]ouabain to the enzyme in microvessels from normotensive and hypertensive rats. The synaptosomal Na+,K(+)-ATPase is sensitive to aluminum. AlCl3 (1-100 microM) inhibits the K(+)-dependent-p-nitrophenylphosphatase (K(+)-NPPase) activity of the Na+,K(+)-ATPase in a dose-dependent manner. AlCl3 (100 microM) decreases the Vmax by 14% but does not alter the KM, suggestive of non-competitive inhibition. The enzyme from aged brain displays a greater Vmax, but shows the same susceptibility to AlCl3 as the enzyme from younger brain. In summary, disruption of the Na+,K(+)-ATPase may underlie, at least in part, abnormalities of nerve and vascular cell function in disorders where elevated concentrations of fatty acids or metal ions are involved.
Mol Chem Neuropathol
PMID:Control of the Na+,K(+)-ATPase under normal and pathological conditions. 810 35

The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3-4 d to 5-7.5 mM aluminum lactate increased glutamine synthetase activity by 100-300% and diminished glutaminase activity by 50-85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations.
Mol Chem Neuropathol 1993 Aug
PMID:A glutamatergic mechanism for aluminum toxicity in astrocytes. 810 2

During the healing phase of a chemical peritonitis, one or several skeletal muscle fibers develop, de novo, in the peritoneum of the adult of weanling rat diaphragm. One week after the initial injury the new muscle fibers are narrow and have central nuclei and cross-striations. The fibers increase progressively in caliber and the nuclei take up a subsarcolemmal location. The newly formed muscle fibers are separated from the intrinsic diaphragmatic muscle by an elastic membrane and by a hand of hyaline connective tissue. They are separated from the peritoneal surface by a zone of granulation tissue. Most new fibers are oriented at right angles to the intrinsic diaphragmatic muscle fibers. Their location and orientation suggest an origin from mesothelium or from fibroblasts in the granulation tissue rather than from the intrinsic diaphragmatic muscle. A similar phenomenon can be induced in the pleura on the other side of the diaphragm. In contrast, damage to the diaphragmatic muscle by injection of aluminum lactate does not engender myogenesis in the location described despite active regeneration in the intrinsic muscle.
Exp Mol Pathol 1994 Feb
PMID:Neogenesis of skeletal muscle in the postinflammatory rat peritoneum. 816 71

Guanosine 5'-O-(thiotriphosphate) (GTP gamma S), an activator of guanine nucleotide binding protein (G protein), increased prostaglandin E2 (PGE2) production in saponin permeabilized rat thymic epithelial cells, TEA3A1. Aluminum fluoride (A1F4-), a cell permeable G protein activator, also stimulated PGE2 production and arachidonic acid (AA) release from TEA3A1 cells. Using A1F4- instead of GTP gamma S as a G-protein activator, we have investigated the mechanism of G-protein mediated stimulation of PGE2 production in TEA3A1 cells. Results from our experiments indicate that G protein mediated activation of AA metabolism in TEA3A1 cells is regulated by two independent mechanisms. One is by the stimulation of AA release via the activation of PLA2 enzymatic activity through PLC and PKC mediated pathway and the other is by a concomitant inhibition of AA incorporation into membrane phospholipids.
Biochem Mol Biol Int 1993 Nov
PMID:Guanine nucleotide-binding protein stimulates arachidonic acid metabolism in TEA3A1 thymic epithelial cells by stimulating release and inhibiting incorporation of arachidonic acid. 829 92

A modified reverse dot-blot assay was developed and used in combination with a nested PCR amplification of hly A for the specific detection of Listeria monocytogenes. The deoxynucleotides and digoxygenin-11-dUTP concentrations in the PCR were optimized for maximal sensitivity and economy. For the dot-blot hybridization, digoxygenin-labelled PCR products were directly spotted on nylon membrane-bound poly-dT tailed capture probes and the signal detection was either colorimetric or chemiluminescent. With crude cell lysates, the total assay could be completed in about 6 h with a detection limit between 2 and 25 colony forming units (cfu) per PCR. The assay was then tested for its applicability to environmental sampling of artificially contaminated aluminum surfaces. For environmental sampling, the assay requires an additional overnight enrichment step and has a sensitivity corresponding to 5 cfu per 25 cm2 of inoculated surface.
Mol Cell Probes 1993 Jun
PMID:A combined modified reverse dot-blot and nested PCR assay for the specific non-radioactive detection of Listeria monocytogenes. 836 65

The B cell antigen receptor complex (BCR) is composed of a membrane-spanning immunoglobulin molecule (mIg) non-covalently associated with heterodimers of the transmembrane proteins Ig-alpha and Ig-beta. The cytoplasmic domains of Ig-alpha and Ig-beta do not contain kinase domains but are phosphorylated on tyrosine residues immediately upon receptor ligation. The mechanism and kinase responsible for initial Ig-alpha and Ig-beta phosphorylation following receptor ligation is unknown, In an attempt to better understand this process, Ig-alpha and Ig-beta phosphorylation was examined in response to treatment of permeabilized B cells with the pharmacologic agents, aluminum fluoride (AlFx) and sodium orthovanadate (Na3VO4). AlFx is known to stimulate GTP-binding proteins while Na3VO4 inhibits protein tyrosine phosphatases (PTPs), both of which are involved in the BCR signalling cascade. In these studies, AlFx and Na3VO4 stimulated rapid tyrosine phosphorylation of Ig-alpha, Ig-beta, and additional cellular proteins, including the protein tyrosine kinase (PTK) Lyn. The tyrosine phosphorylation does not appear to be mediated through GTP-binding proteins, since GTP gamma S did not stimulate tyrosine phosphorylation. As expected, however, PTPs modulate the phosphorylation state of these proteins since another PTP inhibitor, phenylarsine oxide (PAO), increased phosphorylation of Ig-alpha, Ig-beta and other proteins in this system. Interestingly, the extent and kinetics of the mIg-associated Lyn and Ig-alpha/Ig-beta phosphorylation was correlated, suggesting that Lyn may mediate receptor phosphorylation. Alternatively, Lyn, may be a downstream effector of phosphorylated Ig-alpha and Ig-beta as suggested by the reported ability of biphosphorylated Ig-alpha to activate Fyn PTK in vitro. Finally, all components necessary for Na3VO4, but not AlFx, stimulation of phosphorylation are membrane associated. The data are consistent with modulation of phosphorylation of Ig-alpha and Ig-beta through both PTP inhibition and AlFx treatment, and a common intermediary in or effector of these phosphorylation pathways appears to be the Lyn kinase.
Mol Immunol 1995 Nov
PMID:Manipulation of B cell antigen receptor tyrosine phosphorylation using aluminum fluoride and sodium orthovanadate. 855 52

Since desferrioxamine exhibits toxic effects, the possible use of several other therapeutic agents in acute aluminum intoxication has been investigated in this study. The potential for the chelation of aluminum (Al) by different compounds has been first determined using two in vitro techniques. The formation of stable complexes with Al in an aqueous solution has been evaluated by using pulse polarography. This technique allows the influence of temperature and of calcium (Ca) to be studied for each compound. Certain compounds (HEDTA, DTPA) showed extensive chelation in the presence of Ca2+ at a temperature of 37 +/- 1 degree C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy (A.E.S.) has allowed the ability of different substances to complex Al that was previously bound to serum proteins, to be estimated. The kinetics of chelation and the minimum efficient concentration have been determined for all of the products studied. The real efficacies of the compounds were studied by in vivo investigations to compare the effectiveness of the best chelating agents (DFO, HEDTA and EDTA) on the distribution and excretion of Al, after repeated i.p. administration to rats. HEDTA shows a chelation potential as widely active as the DFO potential.
Res Commun Mol Pathol Pharmacol 1995 Jun
PMID:In vitro and in vivo comparative studies on chelation of aluminum by some polyaminocarboxylic acids. 856 84

Addition of 400 microM AlCl3 to the culture medium for 72 h has been previously shown to induce perikaryal whorls of intermediate-sized filaments in intact mouse NB2a/d1 neuroblastoma cells. Immunoblot analyses demonstrated that in vivo treatment of cells with aluminum induced the de novo appearance of extensively phosphorylated NF-H isoforms in cytoskeletons of undifferentiated cells and increased levels of these isoforms in differentiated cells. Neurofilament subunits isolated from intact cells treated with aluminum were resistant to dephosphorylation in vitro by alkaline phosphatase and to in vitro degradation by endogenous calcium-dependent protease(s). These alterations were accompanied by a greater tendency of neurofilaments to form insoluble aggregates after isolation. These findings demonstrate direct effects of aluminum on neurofilament subunits within intact neuronal cells similar to those previously demonstrated following in vitro exposure of isolated neurofilaments to aluminum.
Mol Chem Neuropathol 1995 Sep
PMID:Aluminum treatment of intact neuroblastoma cells alters neurofilament subunit phosphorylation, solubility, and proteolysis. 858 20

We examined the genotoxicity of dichloromethane extracts from 50 final effluent samples collected from 42 industries, including pulp and paper, chemical manufacturing, metal refining, metal surface treatment, and municipal waste water treatment. Effluents were initially fractionated into dissolved substances, and substances adsorbed to suspended particulate matter. Acid/base partitioning was used to further fractionate aqueous extracts. Genotoxicity of extracts was found to be related to sample type, industry type, metabolic activation status, and extract fluorescence (380 nm excitation, 430 nm emission). S9 metabolic activation reduced genotoxic potency in over 90% of the extracts examined. Expression of potency values per equivalent unit of original sample revealed that effluent particulate matter is, on average, almost four orders of magnitude more potent than aqueous filtrates. Suspended particulate matter from organic and inorganic chemical production, petroleum and metal refining, and from metal surface treatment facilities, provided extracts that were significantly more genotoxic than those from sewage treatment and pulp and paper facilities. Aqueous filtrates from inorganic and organic chemical production, metal refining, and surface treatment facilities were significantly more genotoxic than those emitted by aluminum and petroleum refineries. Overall, the results suggest that pulp and paper mills emit mostly soluble genotoxins, while petroleum and aluminum refineries emit predominantly particle-associated genotoxins. Although some extracts elicited a strong SOS response, the potency of the extractable residues was low when compared to highly potent pure substances such as benzo(alpha) pyrene. On average, a mg of dichloromethane-extractable residue has an SOS genotoxicity equivalent to 0.1-1.0 microg of benzo(alpha) pyrene. Predicted Ames mutagenic potency values corresponded reasonably well with industrial waste mutagenic potency values corresponded reasonably well with industrial waste mutagenic potency values published by other researchers. Genotoxic loading values were calculated to quantify the total daily genotoxic emission and potential hazard of each industry. Highest loadings were from sewage treatment, pulp and paper, and metal refining facilities. Highest loading values were the SOS genotoxic equivalent of over 30 kg of benzo(alpha)pyrene per day. The ultimate hazard of genotoxic emissions is not known. Actual hazard assessment is complicated by a poor understanding of the postemission behavior of genotoxins. Exposure of downstream biota is likely substantial.
Environ Mol Mutagen 1996
PMID:Comparing the presence, potency, and potential hazard of genotoxins extracted from a broad range of industrial effluents. 860 65


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