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

Redox inactivation of glutathione reductase involves metal cations, since chelators protected against NADPH-inactivation, 3 microM EDTA or 10 microM DETAPAC yielding full protection. Ag+, Zn2+ and Cd2+ potentiated the redox inactivation promoted by NADPH alone, while Cr3+, Fe2+, Fe3+, Cu+, and Cu2+ protected the enzyme. The Zn2+ and Cd2+ effect was time-dependent, unlike conventional inhibition. Glutathione reductase interconversion did not require dioxygen, excluding participation of active oxygen species produced by NADPH and metal cations. One Zn2+ ion was required per enzyme subunit to yield full NADPH-inactivation, the enzyme being reactivated by EDTA. Redox inactivation of glutathione reductase could arise from the blocking of the dithiol formed at the active site of the reduced enzyme by metal cations, like Zn2+ or Cd2+. The glutathione reductase activity of yeast cell-free extracts was rapidly inactivated by low NADPH or moderate NADH concentrations; NADP+ also promoted rapid inactivation in fresh extracts, probably after reduction to NADPH. Full inactivation was obtained in cell-free extracts incubated with glucose-6-phosphate or 6-phosphogluconate; the inactivating efficiency of several oxidizable substrates was directly proportional to the specific activities of the corresponding dehydrogenases, confirming that redox inactivation derives from NADPH formed in vitro.
Mol Cell Biochem 1991 Mar 13
PMID:Metals are directly involved in the redox interconversion of Saccharomyces cerevisiae glutathione reductase. 186 75

The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X-ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones.
Exp Mol Pathol 1991 Aug
PMID:Cadmium toxicity in the thyroid gland of pregnant rats. 188 72

Cadmium exposure is capable of causing acute and chronic lung injuries, but the specific pathogenetic mechanisms are uncertain. The effects of cadmium ion (Cd2+) on phospholipid metabolism were examined in cultured bovine pulmonary artery endothelial cells (BPAEC), as endothelial cells appear to be particularly vulnerable to the toxic effects of this metallic ion. Exposure of radiolabeled BPAEC to millimolar concentrations of Cd2+ causes liberation of substantial amounts of [3H]arachidonic acid ([3H]AA), but only small amounts of [14C]stearic acid, from each of the major phospholipid subclasses. Analyses of hydrolytic products in BPAEC radiolabeled with [3H]myo-inositol and exposed to Cd2+ indicate that degradation of complex phospholipids is mediated by phospholipase A2. The ability of BPAEC to incorporate fatty acids or lysophosphatides into complex phospholipids is similarly impaired after exposure to Cd2+, suggesting that the liberation of [3H]AA might be due to impairment of reacylation mechanisms and not to increased hydrolytic activity of phospholipase A2. Of the two enzymes involved in reacylation reactions, Cd2+ is found to inhibit the activity of arachidonyl-specific acyl coenzyme A synthetase but not the activity of acyltransferase. Cd2+ also causes a profound time- and dose-dependent depletion of adenosine triphosphate levels in BPAEC, and these changes closely correlate with the liberation of [3H]AA. We suggest that impairment of reacylation mechanisms, and the consequent accumulation of arachidonic acid, may be important in the development of the acute inflammatory reaction that is characteristic of Cd(2+)-induced lung injury.
Am J Respir Cell Mol Biol 1991 Oct
PMID:Cadmium ion-induced alterations of phospholipid metabolism in endothelial cells. 191 Aug 17

Intralobar instillation of cadmium chloride (CdCl2) into the left lungs of rats initiated a sequence of events that culminated in massive unilateral intraluminal fibrosis. Early events (days 1 and 2) after CdCl2 administration included infiltration of the treated lung with polymorphonuclear leukocytes, an increase in the number of alveolar macrophages, activation of the macrophages as assessed by the induction of cathepsin L mRNA, and the induction in liver of mRNA for the acute-phase response protein, alpha 1-acid glycoprotein. By days 5 to 7 in the treated lungs, mRNA for procollagen alpha 1(I) increased 20- to 60-fold, and mRNA for procollagen alpha 1(III) increased 4- to 14-fold. These increases were correlated with the almost complete filling of the alveolar spaces with fibroblasts and collagen. The contralateral lung exhibited no significant change in histology but showed a similar induction of collagen gene expression. These increases were tissue-specific, as the livers of these animals showed no change from the control levels of collagen gene expression. Procollagen messages in the treated and contralateral lungs were equally competent for translation into pro-alpha 1(I) and pro-alpha 2(I) polypeptides. Both the treated and contralateral lungs increased hydroxyproline content about 1.5- to 2-fold over 14 days. The contralateral lung, but not the treated lung, showed a 2-fold increase in lung volume. As a result, the collagen density (mg collagen/ml lung volume) doubled in the treated lung but remained constant in the contralateral lung. These data indicate that CdCl2 caused a rapid induction of pulmonary fibrosis in the treated lungs of rats and stimulated histologically normal growth of the contralateral lung.
Am J Respir Cell Mol Biol 1991 Oct
PMID:Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride. 191 Aug 23

An improved form of crystals of large (50 S) ribosomal subunits from Haloarcula marismortui, formally named Halobacterium marismortui, diffracting to 3 A resolution, has been obtained by the addition of 1 mM-Cd2+ to the crystallization medium, which contained more than 1.9 M of other salts. The improved crystals, grown from functionally active particles to an average size of 0.3 mm x 0.3 mm x 0.08 mm, are isomorphous with the previously reported ones, which diffracted to 4.5 A. They are of space group C222(1), cell dimensions a = 210 A, b = 300 A, c = 581 A, and contain one particle in the asymmetric unit. Their superior internal order is reflected not only in their high resolution, but also in their reasonable mosaicity (less than 0.3 degrees). In contrast to the previously grown crystals, the new ones are of adequate mechanical strength and survive well the shock-cooling treatment. Due to their weak diffracting power, all crystallographic studies have been performed with synchrotron radiation. At cryotemperature, these crystals showed no measurable decay for a few days of irradiation and a complete diffraction data set could be collected from a single crystal. Efforts for initial phasing by specific and quantitative derivatization with super-dense heavy-atom clusters are in progress.
J Mol Biol 1991 Nov 05
PMID:Characterization and preliminary attempts for derivatization of crystals of large ribosomal subunits from Haloarcula marismortui diffracting to 3 A resolution. 194 63

We report the sequence of the Mto gene, one of the two known metallothionein genes of Drosophila melanogaster, and compare its structure with that of the other metallothionein gene, Mtn. The main structural features are the presence of a small intron (61 base-pairs), the presence of four potential MREs (metal regulatory elements) and the absence of a TATA box in the promoter region. Of all metals tested, Hg2+, Cd2+ and Cu2+ are the most efficient ions for inducing an increase in Mto gene transcription. The Mto and Mtn genes are differentially regulated during normal development. Transcription of Mto is detected early in embryogenesis (0 to 3 h) and persists to the third larval instar, while Mtn expression starts later in embryogenesis (12 to 15 h) and is thereafter maintained throughout larval development and adult stages. Sequencing of the Mto protein is in good agreement with the nucleic acid data. Surprisingly, attempts to isolate and characterize the Mtn protein were unsuccessful. Several lines of evidence suggest that this metallothionein is rapidly incorporated after its synthesis into lysosomes, where it would be processed in a way that would not permit its purification. The function of the Mtn protein thus appears to be mainly related to detoxification processes. The pattern of expression of Mto suggests that this gene may be involved in the control of metal homeostasis during development.
J Mol Biol 1990 Sep 20
PMID:Metallothionein Mto gene of Drosophila melanogaster: structure and regulation. 197 15

The in vitro effects of aneuploidogens on taxol-purified microtubules from whole Drosophila melanogaster and mouse brain were studied by a spectrophotometric assay and electron microscopy. Colchicine, acetonitrile, propionitrile, acrylonitrile, dimethylsulfoxide (DMSO), griseofulvin, and cadmium chloride inhibit microtubule assembly, whereas methoxyethyl acetate (MEA) does not. Qualitatively similar results were observed with D. melanogaster and mouse brain microtubules. The in vitro results from D. melanogaster correlate well with previously published results from in vivo assays monitoring induced sex chromosome aneuploidy in that effective aneuploidogens are observed to affect microtubule assembly. The inclusion of taxol does not appear to qualitatively affect the assembly assays with the chemicals tested. In contrast with results from assembly assays, the tested aneuploidogens, including colchicine, do not promote disassembly to taxol-purified microtubules. It is possible that taxol has shifted the equilibrium and stabilized the formed microtubules to the extent that they are no longer sensitive to aneuploidogen-induced disassembly.
Environ Mol Mutagen 1990
PMID:Aneuploidy in Drosophila. III: Aneuploidogens inhibit in vitro assembly of taxol-purified Drosophila microtubules. 197 71

A 3.3 kb fragment of yeast genomic DNA was isolated by screening a genomic library constructed in the high copy number 2 micron plasmid YEp351 vector for clones capable of enhancing the degree of resistance of Saccharomyces cerevisiae strain MW3070-8B to cadmium. The insert contained two complete copies of the CUP1 gene open reading frame (183 bp), including the upstream promoter sequences (450 bp) with two conserved metal responsive cis-acting elements. Northern analysis showed that addition of cadmium (0.02 microM) or copper (50 microM) to overnight liquid cultures of yeast induced expression of CUP1 transcripts from both chromosomal and plasmid-borne gene copies. The cloned 3.3 kb DNA in a high copy number plasmid restored copper resistance to the sensitive strain LS70-3B delta, deleted for the CUP1 gene (cup 1 delta), but failed to restore cadmium resistance. Thus, CUP1 gene expression in yeast appears to be influenced differently by cadmium and copper ions. Resistance to heavy metal poisoning resulted from enhanced gene product levels attributable to amplification of the CUP1 gene as well as to increased transcriptions. Two distinct gene product levels mediate cadmium and copper resistance; a higher gene product level was required to confer cadmium resistance.
Mol Gen Genet 1991 Mar
PMID:Multicopy CUP1 plasmids enhance cadmium and copper resistance levels in yeast. 201 34

A computer-based pattern recognition (PR) approach has been applied to the classification and interrogation of 1H NMR-generated urinalysis data, in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous urinary metabolite were regarded as coordinates in multidimensional space and analyzed using PR methods, through which the dimensionality was reduced for display and categorization purposes. The changes in the NMR spectral patterns were characterized by 17 metabolic dimensions, which were then analyzed by employing the unsupervised learning methods of hierarchical cluster analysis, two-dimensional nonlinear map (NLM) analysis, and two- or three-dimensional principal components analysis (PCA). Different types of toxin (hepatotoxins and cortical and papillary nephrotoxins) were classified according to NMR-detectable biochemical effects. PCA provided consistently better results than NLMs in terms of discrimination of toxicity type, and maps based on correlation matrices also gave improved discrimination over those based on raw data. Various refinements in the data analysis were investigated, including taking NMR urinalysis data at three time points after exposure of the rats to six different nephrotoxins, as well as employing a dual-scoring system (time and magnitude of change). The maps generated from the time-course information produced the best discrimination between nephrotoxins from different classes. The robustness of the classification methods (in particular NLMs and PCA based on correlation matrices) and the influence of the addition of new scored biochemical data, reflecting dose-response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins, the addition of a new toxin class (cadmium chloride, a testicular toxin and renal carbonic anhydrase inhibitor), and an additional metabolite descriptor (creatine), to the PR analysis were also evaluated. Initial training set maps were fundamentally stable to the addition of new data, and both NLM and PCA methods correctly "predicted" the toxicological effects from NMR data for test compounds, suggesting that the approach using PR and 1H NMR urinalysis for the generation and classification of acute toxicological data has wide applicability.
Mol Pharmacol 1991 May
PMID:Application of pattern recognition methods to the analysis and classification of toxicological data derived from proton nuclear magnetic resonance spectroscopy of urine. 203 35

The whole-cell current clamp and voltage clamp techniques were used to record the slow Na+ action potentials (APs) and the inward current in cultured single ventricular cells isolated from young (3 day-old) embryonic chicks. The slow Na+ APs had a +Vmax of 21.5 +/- 7.5 V/s (in 10 different single cells) and the macroscopic inward current responsible for the rising phase of these APs was a fast transient (ft) current. The ft inward current was sensitive to changes in [Na]o but not to changes in [Ca]o. This channel was found to be permeable to Li+ and Ba2+. Analysis of Na+ current decay suggests a second-order process of current decay. The slow Na+ APs and the ft inward current were insensitive to tetrodotoxin (TTX) and Mn2+. This current was also insensitive to the inorganic Ca2+ blockers, Ni2+, Cd2+ and La3+. At low concentration (10(-9)-10(-6) M) the organic Ca2+ blockers, (-)D888 and nifedipine had no effect on the TTX- and Mn2(+)-insensitive INa. However, at a high concentration (10(-5) M), the Ca2+ blockers, (-)D888 and nifedipine, completely blocked the slow Na+ APs and the TTX- and Mn2(+)-insensitive ft inward Na+ current responsible for the rising phase of the APs. High concentration of verapamil (10(-5) M) and D-600 (10(-5) M) had little depressant effects due to their frequency dependence. Apamin, a toxin in the bee venom, that was previously reported by our group to block the slow Ca2+ APs (Bkaily et al., 1985) and the slow Ca2+ current (Bkaily et al., 1988b), greatly decreased the TTX- and Mn2(+)-insensitive ft INa at 10(-10) M. Thus, the inward current responsible for the rising phase of the slow Na+ APs in 3 day-old embryonic chick heart shows fast transient activation and is TTX- and Mn2(+)-insensitive. This channel is highly sensitive to apamin and shares few characteristics with the Ca2+ channel and the TTX-sensitive fast Na+ channel.
J Mol Cell Cardiol 1991 Jan
PMID:Apamin, a highly potent blocker of the TTX- and Mn2(+)-insensitive fast transient Na+ current in young embryonic heart. 203 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>