Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Second virial coefficients and hence covolumes for self-interaction of five proteins, viz. ribonuclease, ovalbumin, bovine serum albumin, catalase and alpha-crystallin, have been determined by analyzing the concentration dependence of the partition coefficient obtained from frontal chromatographic studies on either Fractogel TSK HW55 or porous glass beads. The resulting estimates of the effective radii essentially duplicate their Stokes counterparts and thereby provide further justification for assuming the approximate identity of the thermodynamic and hydrodynamic radii of hydrated globular proteins. Gel chromatographic evaluation of second virial coefficients for protein/dextran systems has led to elimination of the sphere/sphere model as a valid thermodynamic description of the space-filling effects in protein/polymer mixtures, since it does not predict the observed independence of covolume, expressed per unit mass of polymer, upon size of the polymer. This requirement is met by the sphere/rod model [Edmond, E. & Ogston, A. G. (1968) Biochem. J. 109, 569-576] and also by the sphere/flexible-segment model [Hermans, J. (1982) J. Chem. Phys. 77, 2193-2203]. Furthermore, similar studies of the effect of solute radius on covolume for interaction with dextran T70 attest to the adequacy of either model for predicting the thermodynamic nonideality arising from the inclusion of dextrans in protein solutions, and also provide the relevant calibration of the model.
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PMID:Thermodynamic nonideality in macromolecular solutions. Evaluation of parameters for the prediction of covolume effects. 237 80

The seco-steroid hormone 1,25-dihydroxyvitamin D3 is known to induce the expression of a calcium binding protein termed calbindin-D28K in a variety of target tissues. In order to comprehend the mechanism of induction we have cloned and sequenced the chicken calbindin-D28K gene. The gene spans some 18.5 kilobases (kb) of chromosomal DNA from the putative Cap site to the polyadenylation site of the 2.8 kb mRNA. It is split into 11 coding exons by 10 intervening sequences. The promoter region of this gene is markedly G + C-rich (60-80%) extending from -225 to +400. Within this region we find 70 CpG dinucleotides, four G-C boxes, and numerous known promoter regulatory signals. These putative regulatory signals include a TATA box (ATAAATA) at -30 and a CAT box (CCAAT) at -326. Ten additional variant CAT boxes are found in the upstream promoter region (-218 to -770) of this gene. Furthermore we have identified a glucocorticoid-like responsive element at -410 (TCTACACACTGTTCC) and this element overlaps a metal responsive element (TGCACTC) and a variant CAT box (CCAAAT) and juxtaposes an enhancer-like core element (AAATGGT) on its 3'-side. In addition, the calbindin-D28K promoter is composed of a variety of simple repeated sequences, some of which are components of putative regulatory signals. All splice junctions were found to conform to the GT-AG rule. A consensus sequence of the 5'-splice junction reads AG/GTAAG-TTATA. A consensus sequence of the 3'-splice site consists of two elements: a pyrimidine track (mainly T) followed by ACAG/G-T. A two-dimensional model of calbindin-D28K was constructed which projects the existence of 6 alpha-helix-loop-alpha-helix regions characteristic of calcium binding domains. The 3'-end of the gene consists of a single large (2039 base pair) uninterrupted exon, an organizational feature common to other members of the calcium binding protein gene family which include calmodulin, parvalbumin, Spec I, myosin light chains, etc. Another feature common to the gene family is the presence of the repeated sequence ATTT or TTTA located in the 3'-untranslated exons. These simple repeat sequences could be involved in regulating mRNA degradation by serving as a ribonuclease recognition signal.
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PMID:Molecular structure of the chicken vitamin D-induced calbindin-D28K gene reveals eleven exons, six Ca2+-binding domains, and numerous promoter regulatory elements. 296 15

The molybdenum requirement for growth and conidial formation by Aspergillus flavus, A. terreus, and A. sulphureus was found to be 0.2 ppb, which was one-fifth that of an A. niger isolate. Molybdenum deficiency depressed growth, conidial formation, dry weight, soluble protein, and the specific activities of nitrate reductase, succinic dehydrogenase, and aconitase in all the isolates of Aspergillus studied, but the specific activities of catalase and peroxidase were depressed only in isolates of A. niger, A. terreus, and A. flavus. Also, molybdenum deficiency stimulated the specific activities of acid phosphatase and ribonuclease in the A. flavus isolate, although the specific activities of these enzymes decreased in other isolates. Eighteen hours after the addition of molybdenum (5 ppb) to molybdenum-deficient (0.02 ppb) cultures of A. niger, the specific activities of catalase, peroxidase and succinic dehydrogenase were restored in the absence of cycloheximide, while the specific activity of nitrate reductase was recovered even in the presence of the inhibitor. There was no effect on the specific activities of aconitase and acid phosphatase following the addition of molybdenum to molybdenum-deficient cultures of A. niger.
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PMID:Molybdenum nutrition of isolates of four Aspergillus species. 309 Dec 28

Human blood leukocytes and platelets and mouse peritoneal macrophages emit very rapid and very intense Luminol-dependent chemiluminescence (CL) signals when treated with streptococci, staphylococci, or with zymosan, which have been preopsonized with arginine-rich histone, dextran sulfate or polyanetholesulfonate (liquoid). Liquoid alone at 10-30 micrograms/2 X 10(5) leukocytes also triggers intense CL responses in the absence of a carrier. Strong CL can also be triggered, and at the same levels, when the various polyelectrolytes are simply mixed with the bacteria or zymosan and added to the leukocyte suspensions. The CL responses induced by the polyelectrolyte-bacteria complexes greatly exceed those triggered in leukocytes by antibody-complement-coated particles. Liquoid also shows a unique property of markedly augmenting CL signals which have already been induced by other ligand-coated bacteria or zymosan particles. Streptococci and staphylococci were found to be much superior to zymosan, Gram-positive bacilli, or E. coli as carriers for the various polyelectrolytes in the CL reaction. Neither protamine sulfate, lysozyme, myeloperoxidase, crystalline ribonuclease (all cationic in nature), chondroitin sulfate, heparin, nor alginate sulfate acted as ligands for triggering CL, when used to opsonize bacteria or zymosan. The induction of CL in blood leukocytes by the various ligand-coated bacteria is markedly inhibited by azide, KCN catalase, aminotriazole, and EDTA, agents known to inhibit the production of oxygen radicals following stimulation of leukocytes by opsonized bacteria. Two children diagnosed for chronic granulomatous diseases (CGD) of childhood and an apparently healthy sister of one of the male patients completely failed to respond with CL either to the polyelectrolyte-bacteria complexes, liquoid or antibody-coated bacteria and zymosan. It is proposed that liquoid be employed for the rapid screening of defects in certain oxygen-dependent metabolic processes in both PMNs and macrophages. It is also suggested that polyelectrolytes like the ones described in this study may markedly enhance the bactericidal properties of leukocytes and macrophages towards both extracellular and intracellular microorganisms and may perhaps also augment the tumoricidal effects of activated macrophages.
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PMID:Bacteria and zymosan opsonized with histone, dextran sulfate, and polyanetholesulfonate trigger intense chemiluminescence in human blood leukocytes and platelets and in mouse macrophages: modulation by metabolic inhibitors in relation to leukocyte-bacteria interactions in inflammatory sites. 618 6

Presence of carbonate anions increases the oxidation of luminol in different chemical systems. Lysis of human erythrocytes due to the action of dihydroxyfumaric acid or of perborate is also stimulated by carbonate ions. These anions also change considerably the loss of activity of different enzymes treated with superoxide, hydroxyl or formate radicals and can increase or decrease the effect as a function of the nature of the active centre of the enzyme. The relative effects of superoxide, hydroxyl, formate and carbonate radicals for the inactivation of various enzymes (superoxide dismutases, catalase, ribonuclease, glucose oxidase and glutathione peroxidase) have been examined. Three systems were used: gamma-irradiation under different conditions, photoproduction of radicals and sonication. Inactivation of the enzymes is a function not only of the radical used but also of the nature of the active site. Thus glutathione peroxidase is remarkably resistant to hydroxyl radicals while the superoxide dismutases are rapidly inactivated by carbonate radicals. All of the results combine to show that the presence or absence of carbonate anions must be considered in all studies of oxygen containing free radicals whether chemical, biochemical or biological or high energy irradiation.
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PMID:Carbonate anions; effects on the oxidation of luminol, oxidative hemolysis, gamma-irradiation and the reaction of activated oxygen species with enzymes containing various active centres. 630 56

Studies in animal models suggest that oxygen radicals are important in the pathogenesis of acute pancreatitis. Cerulein, a decapeptide isolated from the skin of the frog, Hyla caerula, is closely related to the C-terminus of cholecystokinin and it is a potent stimulant of pancreatic exocrine secretion. The aim of the present study was to measure the activity of endogenous scavengers, superoxide dismutase, catalase and glutathione levels in cerulein-induced acute pancreatitis in rats. We found that the plasma amylase and ribonuclease levels in the pancreatitis group were both significantly high (p < 0.01, p < 0.05, respectively) when compared with the control group. Although superoxide dismutase and glutathione levels of pancreatic tissue were decreased significantly (p < 0.01, p < 0.01 respectively), we observed a significant increase (p < 0.01) in catalase activity in the cerulein treated group compared to the control group. Therefore, we concluded that the profound alteration of the activities of endogenous scavengers (superoxide dismutase, catalase) and glutathione depletion occurring after cerulein-induced pancreatitis seemed to be important in tissue injury and may provide the basis for successful therapy of the disease.
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PMID:The endogenous scavengers in cerulein-induced acute pancreatitis. 754 30

Procedures are described for linking monomethoxypoly(ethylene glycol) (mPEG) to both epsilon and alpha amino groups of lysine. The lysine carboxyl group can then be activated as a succinimidyl ester to obtain a new mPEG derivative (mPEG2-COOSu) with improved properties for biotechnical applications. This branched reagent showed in some cases a lower reactivity toward protein amino groups than the linear mPEG from which it was derived. A comparison of mPEG- and mPEG2-modified enzymes (ribonuclease, catalase, asparaginase, trypsin) was carried out for activity, pH and temperature stability, Km and Kcat values, and protection to proteolytic digestion. Most of the adducts from mPEG and mPEG2 modification presented similar activity and stability toward temperature change and pH change, although in a few cases mPEG2 modification was found to increase temperature stability and to widen the range of pH stability of the adducts. On the other hand, all of the enzymes modified with the branched polymer presented greater stability to proteolytic digestion relative to those modified with the linear mPEG. A further advantage of this branched mPEG lies in the possibility of a precise evaluation of the number of polymer molecules bound to the proteins; upon acid hydrolysis, each molecule of mPEG2 releases a molecule of lysine which can be detected by amino acid analysis. Finally, dimerization of mPEG by coupling to lysine provides a needed route to monofunctional PEGs of high molecular weight.
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PMID:A branched monomethoxypoly(ethylene glycol) for protein modification. 771 Nov 5

Detoxification of host plant defensive compounds by larval Lepidoptera is mediated by cytochrome P450 monooxygenases (P450s) such as CYP6B1, which is expressed in Papilio polyxenes (black swallowtail) larvae in response to xanthotoxin, a linear furanocoumarin. Baculovirus-mediated expression of two cloned CYP6B1 cDNAs in lepidopteran cell lines has demonstrated that CYP6B1 isozymes primarily metabolize the linear furanocoumarins, xanthotoxin and bergapten, and not angular furanocoumarins. To characterize the regulatory features of the CYP6B1 transcription unit, we have isolated the first full-length CYP6B1v3 genomic DNA clone from P. polyxenes. The open reading frame of this gene is interrupted by a single intron and is virtually identical to the previously characterized CYP6B1 cDNAs. Primer extension and ribonuclease protection analyses have localized the transcription initiation site to a point 28 nucleotides upstream from the AUG initiation codon. RNase protection analyses on RNA from larvae induced by linear and angular furanocoumarins indicate that transcription of the CYP6B1 gene is induced in insects significantly in response to xanthotoxin and only slightly in response to bergapten. Angular furanocoumarins, such as angelicin, which are not appreciably metabolized by the CYP6B1 gene product, do not significantly induce transcription of this gene. We conclude that this P450 gene is transcriptionally regulated in vivo by at least one of the substrates which the encoded protein metabolizes. Transient expression of CAT fusion constructs in transfected Sf9 lepidopteran cells demonstrates that nucleotides -1 to -838 upstream from the CYP6B1v3 transcription initiation site retain basal and xanthotoxin-inducible transcriptional activities in this heterologous cell line. These data clearly indicate that P. polyxenes has adapted to the presence of furanocoumarins in its host plants by evolving P450 isozymes and regulatory cascades which respond to specific toxins.
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PMID:Transcriptional regulation of the Papilio polyxenes CYP6B1 gene. 806 37

Using a rat S100A1 cDNA probe, S100A1 expression has been documented in rat C6 glioma cells, a cell line previously thought to express only the S100B protein. To identify the molecular mechanisms which target S100A1 gene expression to specific cell types, the rat S100A1 gene was cloned, and functional analysis of the 5' flanking region of the gene was performed. The rat S100A1 gene was located in an 8.5 kb BamHI genomic fragment which contained 3 exons plus 1.6 kb of 5'-upstream and 0.37 kb of 3'-downstream flanking sequence. A single transcription initiation start site and a single polyadenylation signal were identified in this gene. A number of potential regulatory consensus sequences were identified in the rat S100A1 gene including general transcription factor binding sequences (TATA box, GC box and CCAAT box), cAMP regulated sequences (CRE), skeletal muscle specific sequences (E-box and M-CAT), an S100 protein element, and a (GCT) trinucleotide repeat. Analysis of an S100A1 promoter-CAT construct by ribonuclease protection assay demonstrated that this gene is functional in three S100A1 expressing cell lines, C6 cells, PC12 cells and L6 cells. CAT constructs containing progressive deletions of the S100A1 promoter region revealed a positive regulatory element in skeletal muscle (L6) cells between -1600/-1081. The fact that these same sequences were negative in glial (C6) cells and neutral in neuronal (PC12) cells suggests that this region plays a major role in targeting S100A1 expression to specific cell types. The -1081/+10 region contained both positive and negative elements, some of which were cell-type specific. Thus, S100A1 expression is under complex transcriptional control which involves positive and negative elements as well as cell type specific elements.
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PMID:Expression of the rat S100A1 gene in neurons, glia, and skeletal muscle. 879 2

1 The role of nitric oxide (NO) derived from constitutive and inducible nitric oxide synthase (cNOS and iNOS) and its relationship to oxygen-derived free radicals and prostaglandins (PG) was investigated in a carrageenan-induced model of acute hindpaw inflammation. 2 The intraplantar injection of carrageenan elicited an inflammatory response that was characterized by a time-dependent increase in paw oedema, neutrophil infiltration, and increased levels of nitrite/nitrate (NO2-/NO3-) and prostaglandin E2(PGE2) in the paw exudate. 3 Paw oedema was maximal by 6 h and remained elevated for 10 h following carrageenan administration. The non-selective cNOS/iNOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) given intravenously (30-300 mg kg-1) 1 h before or after carrageenan administration, inhibited paw oedema at all time points. 4 The selective iNOS inhibitors, N-iminoethyl-L-lysine (L-NIL) or aminoguanidine (AG), failed to inhibit carrageenan-induced paw oedema during the first 4 h following carrageenan administration, but inhibited paw oedema at subsequent time points (from 5-10 h). iNOS mRNA was detected between 3 to 10 h following carrageenan administration using ribonuclease protection assays. iNOS protein was first detected 6 h and was maximal 10 h following carrageenan administration as shown by Western blot analysis. Administration of the iNOS inhibitors 5 h after carrageenan (a time point where iNOS was expressed) inhibited paw oedema at all subsequent time points. Infiltrating neutrophils were not the source of iNOS since pretreatment with colchicine (2 mg kg-1) suppressed neutrophil infiltration, but did not inhibit the iNOS mRNA expression or the elevated NO2-/NO3- levels in the paw exudate. 5 Inhibition of paw oedema by the NOS inhibitors was associated with attenuation of both the NO2-/NO3- and PGE2 levels in the paw exudate. These inhibitors also reduced the neutrophil infiltration at the site of inflammation. 6 Recombinant human Cu/Zn superoxide dismutase coupled to polyethyleneglycol (PEGrhSOD; 12 x 10(3) u kg-1), administered intravenously either 30 min prior to or 1 h after carrageenan injection, inhibited paw oedema and neutrophil infiltration, but had no effect on NO2-/NO3- or PGE2 production in the paw exudate. The administration of catalase (40 x 10(3) u kg-1), given intraperitoneally 30 min before carrageenan administration, had no effect on paw oedema. Treatment with desferrioxamine (300 mg kg-1), given subcutaneously 1 h before carrageenan, inhibited paw oedema during the first 2 h after carrageenan administration, but not at later times. 7 These results suggest that the NO produced by cNOS is involved in the development of inflammation at early time points following carrageenan administration and that NO produced by iNOS is involved in the maintenance of the inflammatory response at later time points. The potential interactions of NO with superoxide anion and PG is discussed.
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PMID:Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. 879 51


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