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)

While it is well known that cellular prolyl hydroxylase activity is increased in the presence of ascorbic acid, the mechanism of this modulation is not fully understood. Ascorbic acid is known to generate reactive oxygen radicals which are involved in the regulation of gene expression through mechanisms involving the synthesis of polyADP-ribose in the nucleus. We examined a possible role for this mechanism in modulating prolyl hydroxylase activity in cultures of human fetal (20 week) and neonatal (foreskin) dermal fibroblasts and IMR-90 fibroblasts. The activity of prolyl hydroxylase in these cells increased in the presence of ascorbate. Ascorbate markedly increased the levels of polyADP-ribose synthetase. The increase in prolyl hydroxylase activity was abolished or decreased by inhibitors of polyADP-ribose synthesis. Our studies suggest that ascorbate may regulate the cellular activity of prolyl hydroxylase by activating epigenetic control mechanisms involving polyADP-ribose.
Cell Mol Biol Res 1993
PMID:Regulation of prolyl hydroxylase by ascorbic acid is mediated by polyADP-ribose synthesis. 817 95

The activity lost during storage of a solution of muscle glyceraldehyde 3-phosphate dehydrogenase was rapidly restored on adding a thiol compound, but not arsenite or azide. On treatment with H2O2, the enzyme was partially inactivated and complete loss of activity occurred in the presence of glutathione. Samples of the enzyme pretreated with glutathione followed by removal of the thiol compound by filtration on a Sephadex column showed both full activity and its complete loss on adding H2O2, in the absence of added glutathione. Most of the activity was restored when the H2O2-inactivated enzyme was incubated with glutathione (25 mM) or dithiothreitol (5 mM) whereas arsenite or azide were partly effective and ascorbate was ineffective. The need for incubation for a long time with a strong reducing agent for restoration of activity suggests that the oxidized group (disulfide or sulfenate) must be in a masked state in the H2O2-inactivated enzyme. Analysis by SDS-PAGE gave evidence for the formation of a small quantity of glutathione-reversible disulfide-form of the enzyme. Circular dichroic spectra indicated a decrease in alpha-helical content in the inactivated form of the enzyme. The evidence suggest that glutathione and H2O2 can regulate the active state of this enzyme.
Mol Cell Biochem 1993 Dec 08
PMID:Regulation of the activity of glyceraldehyde 3-phosphate dehydrogenase by glutathione and H2O2. 817 27

The susceptibility to lipid peroxidation induced by an iron-ascorbate system was studied in human erythrocyte membranes (ghost), and measured as thiobarbituric acid reactive substances (TBARS) formed. The male and female subjects were 13 chronic alcoholic patients aged 34-54 who assumed 200-250 g/die of ethanol, and 12 healthy controls aged 23-46. In alcoholics ghost sensitivity to lipid peroxidation was significantly decreased compared with that of the controls. Peroxidation on lipids extracted from the ghosts of both control and alcoholic subjects confirmed an increased resistance to free radical damage of the erythrocyte membranes obtained from alcoholic patients, thus indicating that in alcoholic patients the lipid component is involved in the resistance to free radical damage of erythrocyte membranes. Lipid analysis revealed no significant difference in cholesterol and phospholipid content, nor in the phospholipid classes, of the two groups considered. Nevertheless the fatty acid composition of ghosts from the alcoholic subjects was significantly lower in docosahexaenoic acid content than in the controls, and it is with this in mind we propose the explanation of the results we obtained.
Biochem Mol Biol Int 1993 Aug
PMID:Effects of alcohol abuse: studies on human erythrocyte susceptibility to lipid peroxidation. 822 Feb 33

When bovine serum albumin was exposed to the hydroxyl radical generating system of ascorbate-EDTA-Fe3+ or ascorbate-EDTA-Fe(3+)-H2O2, carbonyl formation occurred. Trolox strongly inhibited the oxidative modification in a dose-dependent manner. The fragmentation and enhancement of the proteolytic susceptibility of bovine serum albumin were induced by HO. only in the presence of O2, while trolox protected the protein against such oxidative modifications. In addition, inactivations of lactate dehydrogenase and creatine kinase induced by the hydroxyl radical were also blocked by trolox.
Biochem Mol Biol Int 1993 Sep
PMID:Inhibition of hydroxyl radical-induced protein damages by trolox. 826 Sep 35

At inflammatory sites, before their processing, antigens are exposed to oxygen free radicals released by activated cells. The effect of hydroxyl radicals (OH.) on the structure of a protein antigen, tetanus toxin (TT) was investigated, as well as the consequences on processing and presentation. A chemical system composed of Fe-EDTA, ascorbate and H2O2 was used to produce physiological amounts of OH. radicals. TT exposed to OH. radicals presented a marked decrease of its intrinsic fluorescence with a concomitant increase of the content of bityrosine, but no fragmentation of the protein was detected by SDS-PAGE. Processing of the modified TT was analysed, by incubating TT at acidic pH with fractions enriched in plasma membranes and lysosomes obtained from a lymphoblastoid cell line (LCL). Proteolysis of OH.-treated TT was less important than proteolysis of native TT, especially upon prolonged incubations. Oxidized TT presented by LCL cells induced a greater proliferation of three different TT specific T cell clones, compared to native TT. When proteolytic digests of TT were presented by fixed LCL cells to a homologous T cell line, the proliferative response obtained in the presence of digests of OH.-treated TT was sustained, even in the case of prolonged proteolysis, whereas the response to digests of native TT fell rapidly. The relative resistance of OH.-treated TT to proteolysis appears thus responsible for its greater presentation to specific T cells, probably by protecting epitopes.
Mol Immunol 1993 Dec
PMID:OH. treatment of tetanus toxin reduces its susceptibility to limited proteolysis with more efficient presentation to specific T cells. 827 77

The apple ripening-related cDNA insert of clone pAP4 (G.S. Ross, M.L. Knighton, M. Lay-Yee [1992] Plant Mol Biol 19: 231-238) has previously been shown to have considerable nucleic acid and predicted amino acid sequence similarity to the insert of a tomato ripening-related cDNA clone (pTOM13) that is known to encode the enzyme 1-aminocyclopropane-1-carboxylate (ACC) oxidase (A.J. Hamilton, G.W. Lycett, D. Grierson [1990] Nature 346: 284-287; A.J. Hamilton, M. Bouzayen, D. Grierson [1991] Proc Natl Acad Sci USA 88: 7434-7437). The cDNA insert from the clone pAP4 was fused between the galactose-inducible promoter and the terminator of the yeast expression vector pYES2. Transformation of Saccharomyces cerevisiae strain F808- with this DNA construct and incubation of the yeast in the presence of D[+]-galactose allowed these cells to convert ACC to ethylene. The transformed yeast converted 1-amino-2-ethylcyclopropane-1-carboxylate isomers to 1-butene with the same 1R,2S-stereoselectivity as achieved by the native ACC oxidase from applies. Both ascorbate and Fe2+ ions stimulated the rate of the production of ethylene from ACC by the transformed yeast, whereas Cu2+ and Co2+ were strongly inhibitory; these are features of ACC oxidase. Northern analysis of the total RNA from nontransformed and transformed yeast showed that the ability to convert the ACC to ethylene was correlated with the synthesis and accumulation of a novel 1.2-kb mRNA that hybridized to the cDNA clone pAP4. We conclude that the cDNA sequence of the clone pAP4 encodes ACC oxidase.
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PMID:Apple ripening-related cDNA clone pAP4 confers ethylene-forming ability in transformed Saccharomyces cerevisiae. 827 33

In this paper we present the structural analysis of the 1-aminocyclopropane-1-carboxylate (ACC) oxidase gene family from Petunia hybrida. Southern blot analysis and restriction endonuclease mapping showed that two cloned regions of the petunia genome contained sequences highly homologous to a previously isolated ACC oxidase cDNA clone. Nucleotide sequencing of these two regions of the genome showed that each contained two tandemly arranged genes designated ACO1, ACO2, ACO3 and ACO4. Comparison of the nucleotide sequences of the cloned genomic regions with the cDNA clone pPHEFE indicated that ACO1 encoded the transcript in 4 exons interrupted by 3 introns. The other three members of the petunia ACC oxidase gene family shared identical intron numbers and positions with ACO1 and their exons were greater than 80% homologous. Nucleotide substitutions and deletions in the ACO2 gene indicate that it likely represents a pseudogene. Overall homology between ACO1 and ACO2 indicates that this gene cluster arose by a more recent duplication event than the gene duplication giving rise to the ACO3 and ACO4 cluster. The 5-flanking sequences share little overall homology between members of this gene family. However, sequences which likely make up the core promoter of these genes including the TATA box are highly homologous. RNA-based PCR amplification of ACC oxidase cDNAs from ethylene-treated corollas and wounded leaves revealed transcripts for ACO1, ACO3 and ACO4 indicating that a least three of these genes are transcriptionally active. The proteins encoded by ACO1, ACO3 and ACO4 share more than 90% identity with one another and more than 70% identity with ACC oxidases from other species. The ACC oxidase proteins share significant sequence homology with other enzymes that require Fe(II) and ascorbate for catalytic activity.
Plant Mol Biol 1993 Dec
PMID:Organization and structure of the 1-aminocyclopropane-1-carboxylate oxidase gene family from Petunia hybrida. 829 80

The effect of palm oil, a widely used vegetable oil, rich in tocotrienols, on peroxidation potential of rat liver was examined. Long-term feeding of rats with palm oil as one of the dietary components significantly reduced the peroxidation potential of hepatic mitochondria and microsomes. As compared to hepatic mitochondria isolated from rats fed control or corn oil-rich diet, those from palm oil-fed group showed significantly less susceptibility to peroxidation induced by ascorbate and NADPH. However, in microsomes, only NADPH-induced lipid peroxidation was significantly reduced in rats fed palm oil rich-diet. Though the accumulation of thiobarbituric acid reactive substances during ascorbate-induced lipid peroxidation in mitochondria from rats fed corn oil-rich diet supplemented with tocotrienol-rich fraction (TRF) of palm oil was similar to that of control rats, the initial rate of peroxidation was much slower than those from control or corn oil fed diets. Our in vitro studies as well as analyses of co-factors related to peroxidation potential indicated that the observed decrease in palm oil-fed rats may be due to increased amount of antioxidants in terms of tocotrienol as well as decrease in the availability of substrates for peroxidation.
Biochem Mol Biol Int 1993 May
PMID:Influence of palm oil or its tocotrienol-rich fraction on the lipid peroxidation potential of rat liver mitochondria and microsomes. 835 28

Recent studies have focussed on the role of thiol rich proteins especially metallothionein (MT) in the therapeutic interventions against oxidative damage. In our previous communication we showed that reactive oxygen species arising via Fenton's reactions are the proximal lipid oxidant during nickel-toxicity. The purpose of the present communication is to evaluate the role of zinc, cadmium or silver-metallothioneins on the protection against nickel-induced peroxidative damage. Our results demonstrate that Zn-MT provided maximum protection against nickel-induced mortality in mice and also served as an efficient antagonist in inhibiting nickel-mediated lipid peroxidation compared to Cd-MT or Ag-MT. Zn-MT also provided protection against iron (II)-ascorbate induced microsomal lipid peroxidation and reversed nickel-mediated inhibition of calcium sequenstration. We conclude that Zn-MT could serve as an excellent physiological antioxidant against nickel-mediated oxidative.
Biochem Mol Biol Int 1993 Jun
PMID:Protective role of metallothionein in nickel induced oxidative damage. 836 8

Y79 human retinoblastoma cells have a high capacity to reduce ascorbate autooxidation rates through the reduction of the ascorbate free radicals generated in the oxidation process. Responsible of this capacity is a plasma membrane redox system, which might be functionally related to the Na+/H+ antiporter. Ascorbate has cytotoxic effect on Y79 cells in long-term incubations in the presence of limited amounts of serum in the medium.
Biochem Mol Biol Int 1993 Apr
PMID:A plasma membrane redox system in human retinoblastoma cells. 838 32


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