Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Control of the rate of cardiac cell division by oxygen occurs most probably by altering the redox state of a control substance, e.g. NAD(+)right harpoon over left harpoonNADH. NAD(+) (and not NADH) forms poly(ADP-ribose), an inhibitor of DNA synthesis, in a reaction catalysed by poly(ADP-ribose) polymerase. Lower partial pressure of oxygen, which increases the rate of division, would shift NAD(+)-->NADH, decrease poly(ADP-ribose) synthesis, and increase DNA synthesis. Chick-embryo heart cells grown in culture in 20% O(2) (in which they divide more slowly than in 5% O(2)) did exhibit greater poly(ADP-ribose) polymerase activity (+83%, P<0.001) than when grown in 5% O(2). Reaction product was identified as poly(ADP-ribose) by its insensitivity to deoxyribonuclease, ribonuclease, NAD glycohydrolase, Pronase, trypsin and micrococcal nuclease, and by its complete digestion with snake-venom phosphodiesterase to phosphoribosyl-AMP and AMP. Isolation of these digestion products by Dowex 1 (formate form) column chromatography and paper chromatography allowed calculation of average poly(ADP-ribose) chain length, which was 15-26% greater in 20% than in 5% O(2). Thus in 20% O(2) the increase in poly(ADP-ribose) formation results from chain elongation. Formation of new chains also occurs, probably to an even greater degree than chain elongation. Additionally, poly(ADP-ribose) polymerase has very different K(m) and V(max.) values and pH optima in 20% and 5% O(2). These data suggest that poly(ADP-ribose) metabolism participates in the regulation of heart-cell division by O(2), probably by several different mechanisms.
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PMID:Poly(adenosine dephosphate ribose) metabolism and regulation of myocardial cell growth by oxygen. 2 65

The NAD-glycohydrolase activity of freshly isolated adult rat liver cells nuclei was studied as affected by the ionic (dodecyl sulphate and deoxicholate) and non-ionic (Triton X-100 and digitonin) detergents as well as by ultrasound (15 and 22 kHz). The obtained data permit the detergents to be divided according to the character of their effects on the nuclear NADase activity into "decreasing" and "increasing" ones. Dodecyl sulphate and to a less extent deoxicholate are in the first group of the detergents. Triton X-100 and much more digitonin are in the second one. Sonification of the rat liver cells nuclei (15 and 22 kHz) from 3-10 s and further induced a decrease in the NADase activity with its subsequent complete loss. The treatment of the intact nuclei suspension with DNase leads to a 50% decrease in the NADase activity and the treatment of the sonificated nuclei suspension-- to a complete loss of the activity. Undet these conditions RNase does not affect the NADase activity.
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PMID:[Effect of detergents and ultrasound on NAD-glycohydrolase activity in rat liver cell nuclei]. 17 61

The levels of several enzymes have been studied during sporulation of Saccharomyces cerevisia. The specific activities of ribonuclease and aminopeptidase I raised several-fold after transfer of the cells to sporulation medium, whereas the specific activities of phosphofructokinase, glucose-6-phosphate dehydrogenase, tryptophan synthase and pyruvate decarboxylase were not significantly altered. The specific activities of NAD-dependent glutamate dehydrogenase, isocitrate lyase, malate dehydrogenase and fructose bisphosphatase all decreased from the onset of sporulation. The inactivation of these latter enzymes was inhibited by cycloheximide and by inhibitors of energy metabolism. Hexokinase, alcohol dehydrogenase and glutamate oxaloacetate transaminase were partially lost from the cells during the period of ascus maturation. None of the enzyme changes observed proved to be 'sporulation-specific' in that it occurred exclusively in sporulating diploid yeast cells. Therefore it is postulated that the meiotic events and the metabolic changes required for ascospore formation are under separate genetic control in this organism. During sporulation, the cellular content of cytochromes b, c, and aa3 was reduced to 20% or less of that present in vegetative derepressed cells. Since the relative percentage of total to cycloheximide-insensitive mitochondrial protein synthesis was not significantly altered throughout sporulation, and the pattern of mitochondrially synthesized polypeptides was rather similar both in vegetative and in sporulating cells, it appeared that not only degradation but also synthesis and therefore turnover of the mitochondrially coded polypeptides of cytochromes b and aa3 took place during sporulation. The activity ratio of cytochrome c oxidase to F1-ATPase in submitochondrial particles isolated from vegetative cells and from purified asci was almost identical. This indicates that the loss of membrane-bound mitochondrial cytochromes during sporulation is probably due to a nonselective degradation of inner mitochondrial membrane proteins.
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PMID:Protein degradation during yeast sporulation. Enzyme and cytochrome patterns. 18 44

Ribonuclease activity in HeLa cell nuclei is markedly inhibited by ADP-ribosylation following incubation of intact isolated nuclei with [14C]NAD. Time course experiments demonstrate that [14C] incorporation into proteins is accompanied by a 50% inhibition of ribonuclease activity on single-strand and double-strand polynucleotides. Inhibition does not occur when 3-aminobenzamide, a potent (ADP-ribose) polymerase inhibitor, is present. Two enzymatic activities that degrade double-strand polynucleotides have been purified and partially characterized. A relevant level of radioactivity resulting from [14C]NAD incubation of nuclei was associated to the purified enzyme. The RNase F1 component, which shows maximal activity on polyU-polyA is demonstrated to be the major ADP-ribose acceptor protein.
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PMID:In vitro inhibition of HeLa cell nuclear ribonucleases by ADP-ribosylation. 211 91

Poly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [3H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase. Basal activities in both lymphoma lines were 3-4-fold greater than in mouse L1210 leukaemia cells. However, total endogenous poly (ADP-R) polymerase activity in both L5178Y cell lines, stimulated by a large excess of DNase in the presence of Triton X-100, was less than half the activity in L1210 cells. Doses of N-methyl-N-nitrosourea (MNU) that produced 20-50% survival of colony-forming units increased poly (ADP-R) in both lymphoma lines by only 25% compared with 377% in L1210 cells when synthesis was measured immediately after a 30-min exposure of MNU. During the first 24 h after MNU AII cells produced a peak of activity that was not seen with LS cells. A second peak was seen in both cell lines between 24 and 48 h following MNU. Concentrations of 3-aminobenzamide (3AB) above 2.5 mM inhibited colony-forming ability of lymphoma cells and equally inhibited uptake of [14C]formate into protein, RNA and DNA indicating that 3AB behaves as a general metabolic poison. Concentrations of 3AB in the toxic range of 3-10 mM inhibited poly (ADP-R) synthesis but no degradation of the polymer was observed. Non-toxic concentrations of 3AB potentiated cell killing by MNU to a similar degree in both lymphoma cell lines. In conclusion, we have found little evidence to support the hypothesis that the differential sensitivity of LS and AII is related to poly ADP-ribosylation. Compared with other mouse cells, L5178Y cells appear deficient in poly (ADP-R) polymerase and poly (ADP-R) glycohydrolase activities.
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PMID:Poly (ADP-ribose) metabolism in alkylated mouse L5178Y cells. 299 Jul 53

Reorganization and activation energies for charge transfer reactions occurring inside a dielectric sphere have been calculated by solving the problem of polar medium reorganization within and outside a dielectric sphere placed in another infinite dielectric. The dielectric sphere is assumed to simulate a protein globule, i.e. an enzyme molecule. It has been shown that for some reaction types the activation energy tends to decrease as the globule radius increases and that for each of the reaction types considered there is an optimal globule radius an increase of which does not bring about any tangible activation energy reduction. The calculated optimal radii for different processes are in good agreement with the increasing molecular sizes in the series: ribonuclease less than or equal to lysozyme less than serine proteinases approximately equal to cysteine proteinases less than NAD-dependent dehydrogenases. The calculated radii are usually about 1.5 to 1.7 times (and molecular masses about 4-5 times) smaller than the experimental ones. The reasons for this discrepancy are discussed and it has been suggested that the approximate nature of the treatment of a protein globule as a structureless dielectric is the main reason. It is shown that charge transfer at an acute angle to the globule surface is the optimum process. For endoergonic reaction stages it is the net charge transfer towards the periphery and for exoergonic ones that in the reverse direction which are advantageous. These conclusions are consistent with the data about the structure of the above-mentioned enzymes.
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PMID:Medium reorganization energy and enzymatic reaction activation energy. 315 27

The mechanism of poly ADPR synthesis and the transfer of poly ADPR to histone H1 molecule by electrophoretically homogenous calf thymus poly ADPR polymerase containing DNA was examined. 1) An acid insoluble radioactive complex (I) was obtained after incubation of purified enzyme with [3H] NAD. The stability of (I) was examined by SDS-polyacrylamide gel electrophoresis. The complex (I) was stable against acid, SDS, urea, DNase and RNase, but labile against pronase, trypsin, alkali and snake venom phosphodiesterase treatment. The molecular weight of (I) was about 130 000 daltons estimated by SDS-gel electrophoresis. The radioactive products of successive alkali, venom phosphodiesterase and Pronase hydrolysis of (I) were PR-AMP and AMP. The mean chain length of poly ADPR of (I) was 20--30. These results suggest that the complex (I) is poly ADP-ribosylated poly ADPR polymerase. 2) Besides (I), a second radioactive peak (II) was observed when acid insoluble products obtained from an incubation mixture containing purified poly ADPR polymerase, [3H] NAD and purified histone H1 were analyzed on SDS-polyacrylamide gel electrophoresis. The molecular weight of (II) was estimated to be about 23 000 daltons. The complex (II) is eluted like histone H1 on CM-cellulose columns and hydrolyzed by alkali, trypsin and snake venom phosphodiesterase but not by DNase, or RNase. The comples (II) was extracted selectively by 5 per cent perchloric acid or 5 per cent trichloroacetic acid from mixture of (I) and (II). The mean chain length of poly ADPR of complex (II) and 5--20; these results suggest that the complex (II) is poly ADP-ribosylated histone H1. 3) Results 1) and 2) indicate that purified DNA containing, thus DNA independent, poly ADPR polymerase catalyzes two different reactions, the ADPR transfer onto the enzyme itself and onto histone H1 and the elongation of ADPR chains. Dimeric forms of ADP-ribosylated histone H1 was not observed. Free poly ADPR was observed only when very small quantities of enzyme were used for incubation.
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PMID:Adenosine diphosphate ribosylation of histone H1 by purified calf thymus polyadenosine diphosphate ribose polymerase. 624 65

The effect of thyrotropin (TSH) on the ADP-ribosylation of endogenous thyroid cell acceptor proteins was examined. Cells were "permeabilized" at 4 degrees C in hypotonic medium and then exposed to [(32)P]- or [(3)H-adenine]NAD(+). The net incorporation of labeled ADP-ribose was measured by trichloroacetic acid precipitation. TSH (100 mU/ml) enhanced ADP-ribosylation with a maximum effect after 30-60 min in the majority of experiments. TSH stimulation was observed even when the incubation contained 1,000-fold more exogenous NAD(+) than the amount of NAD(+) contributed by the permeabilized cells, indicating an effect on enzymatic activity rather than an alteration in NAD(+) pool size or specific activity. No incorporation of radioactivity from labeled NAD(+) was observed in cells not rendered permeable to NAD(+) by hypotonic shock. TSH did not increase the rate of disappearance of trichloroacetic-precipitable radioactivity and did not contain intrinsic NAD(+) glycohydrolase activity. Alkali and snake venom phosphodiesterase, but not ribonuclease or deoxyribonuclease digestion of trichloroacetic acid precipitable thyroid cell radioactivity, revealed primarily 5'-AMP, consistent with an effect of TSH on mono-ADP ribosylation. Nicotinamide and thymidine (50 mM) inhibited both basal and TSH-stimulated ADP-ribosylation of thyroid cell protein. Dibutyryl cyclic (c)AMP (0.1 mM) inhibited endogenous ADP-ribosylation by approximately 35% but had no effect at lower concentrations. 0.5 mM isobutylmethylxanthine inhibited this reaction by approximately 60%. We suggest that TSH enhances thyroid cell ADP-ribosylation by a mechanism independent of cAMP as a second messenger, and that ADP-ribosylation plays a role in the expression of TSH.
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PMID:Hormonal stimulation of eucaryotic cell ADP-ribosylation. 626 5

A retinol dehydrogenase, RoDH(1), which recognizes holo-cellular retinol-binding protein (CRBP) as substrate, has been cloned, expressed, and identified as a short-chain dehydrogenase/reductase (Chai, X., Boerman, M. H. E. M., Zhai, Y., and Napoli, J. L. (1995) J. Biol. Chem. 270, 3900-3904). This work reports the cloning and expression of a cDNA encoding a RoDH isozyme, RoDH(II). The predicted amino acid sequence verifies RoDH(II) as a short-chain dehydrogenase/reductase, 82% identical with RoDH(I). RoDH(II) recognized the physiological form of retinol as substrate, CRBP, with a Km of 2 mM. Similar to microsomal RoDH and RoDH(I), RoDH(II) had higher activity with NADP rather than NAD, was stimulated by ethanol and phosphatidyl choline, was not inhibited by the medium-chain alcohol dehydrogenase inhibitor 4-methylpyrazole, but was inhibited by phenylarsine oxide and the short-chain dehydrogenase/reductase inhibitor carbenoxolone. Northern blot analysis detected RoDH(I) and RoDH(II) mRNA only in rat liver, but RNase protection assays revealed RoDH(I) and RoHD(II) mRNA in kidney, lung, testis, and brain. These data indicate that short-chain dehydrogenases/reductase isozymes expressed tissue-distinctively catalyze the first step of retinoic acid biogenesis from the physiologically most abundant substrate, CRBP.
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PMID:Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I. 749 45

NAD is normally regarded as a redox molecule or as the substrate for ADP-ribosylation reactions. In this study, we describe the rapid metabolism of NAD by Percoll-gradient-purified lettuce chloroplasts and show that the adenine moiety can be incorporated into RNA in a dark-activated reaction that senses the redox state of the cytochrome b6f complex. Isolated chloroplasts rapidly metabolised radiolabelled NAD+ to 5'-AMP (within seconds) and adenosine during a 60-min incubation in vitro; the products were analysed by high-performance liquid chromatography. No radiolabelled ADP-ribose was detected. Radioactivity was incorporated into trichloroacetic-acid-insoluble material during this period, with approximately 2-4-fold more incorporation occurring in the dark. Most of this radiolabel was rendered acid-soluble by dilute alkaline digestion at 37 degrees C, yielding an approximately equal mixture of 2'-AMP and 3'-AMP, and by RNase digestion, identifying the acid-insoluble radioactive material as RNA. Protein-bound ADP-ribose would have yielded 5'-AMP and/or oligomeric/polymeric ADP-ribose after alkali digestion. The utilisation of NAD metabolites for RNA synthesis was restricted to the thylakoid compartment of the chloroplast. The use of a variety of electron-transport inhibitors such as 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, bromanil (tetrabromo-1,4-benzoquinone), electron donors (dithiothreitol), electron acceptors (ferricyanide) and an uncoupler showed that the incorporation of radiolabel from NAD into acid-insoluble material was favoured when the cytochrome b6f complex was in the oxidised state (as pertaining to incubations in the dark).
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PMID:NAD turnover and utilisation of metabolites for RNA synthesis in a reaction sensing the redox state of the cytochrome b6f complex in isolated chloroplasts. 750 45


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