Ribonucleic acid synthesis inhibition

Jordan, D. C. and Inniss, W. E. (1959) Selective inhibition of ribonucleic acid synthesis in Staphylococcus aureus by vancomycin. Nature 184 (SuppI 24), 1894-1895. 

POLATNICK, J., AfiLINGHAUS, R.B., GRAVES, J.H. and COWAN, K.M. Inhibition of cell-free foot-and-mouth disease virus ribonucleic acid synthesis by antibody. Virology (I967), 21> 6O9-6I5. 

C37 Cox, R., Martin, J. T. and Shinozuka, H. Studies on acute methionine toxicity. II. Inhibition of ribonucleic acid synthesis in guinea pig liver by methionine and ethionine. Lab. Invest., 29, 54-59 (1973)... 

Wilson, D. E., 1968, Inhibition of host-cell protein and ribonucleic acid synthesis by Newcastle disease virus, J. Virol. 2 1. 

Rifaximin is a synthetic rifamycin derivative, which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis [48]. It is virtually unabsorbed after oral administration and is, therefore, used primarily to treat gastrointestinal infections. Rifaximin possesses a broad spectrum of antimicrobial activity, covering Gram-positive and Gram-negative bacteria, both arerobic and anaerobic [49], Several studies [44, 49-62] have shown that in patients with HE rifaximin displays an efficacy similar to that of lactulose and neomycin (table 1). A recently published study [62] compared the efficacy and safety of... 

Deoxyribonucleic acid (DNA) serves as a template for the synthesis of nucleic acids. Ribonucleic acid (RNA) executes protein synthesis and thus permits cell growth. Synthesis of new DNA is a prerequisite for cell division. Substances that inhibit reading of genetic information at the DNA template damage the regulatory center of cell metabolism. The substances listed below are useful as antibacterial drugs because they do not affect human cells. 

All corticosteroids have the same general mechanism of action they traverse cell membranes and bind to a specific cytoplasmic receptor. The steroid-receptor complex translocates to the cell nucleus, where it attaches to nuclear binding sites and initiates synthesis of messenger ribonucleic acid (mRNA). The novel proteins that are formed may exert a variety of effects on cellular functions. The precise mechanisms whereby the corticosteroids exert their therapeutic benefit in asthma remain unclear, although the benefit is likely to be due to several actions rather than one specific action and is related to their ability to inhibit inflammatory processes. At the molecular level, corticosteroids regulate the transcription of a number of genes, including those for several cytokines. 

In vitro genotoxicity studies are summarized in Table 2-17. Eukaryotic cell systems were used for detecting the effects of 2,3,7,8-TCDD exposure on DNA. Exposure to 2,3,7,8-TCDD did not stimulate the unscheduled DNA synthesis in cultural human cells (Loprieno et al. 1982), but inhibited DNA, ribonucleic acid (RNA), and protein synthesis in mouse lymphocytes (Luster et al. 1979) caused gene mutations in mouse lymphoma cells (Rogers et al. 1982) and induced sister chromatid exchanges in Chinese hamster cells (Toth et al. 1984). 

Mauer RA (1982a) Thyroid hormone specifically inhibits prolactin synthesis and decreases prolactin messenger ribonucleic acid levels in cultured pituitary cells. Endocrinology 770 1507-1514. 

Heme synthesis is controlled by a regulatory negative feedback loop in which heme inhibits the activity of fer-rochelatase and acquisition of iron fi om the transport protein transferrin. The decrease in iron acquisition leads to a decrease in iron uptake into the cell with subsequent decrease in 8-aminolevulinic acid and heme production. Iron deficiency and increased erythropoietin synthesis lead to the combination of the iron regulatory proteins with the iron-responsive elements in the transferrin receptor protein messenger ribonucleic acid (mRNA). This combination in turn leads to protection of the mRNA from degradation with subsequent increased uptake of iron into erythroid cells because of the increased expression of transferrin receptors on the cell membrane. 

Floxuridine is a pyrimidine antimetabolite with its primary effect to interfere with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibit the formation of ribonucleic acid (RNA). It is indicated in palliative management of GI adenocarcinoma metastatic to the liver administered by continuous regional intra-arterial infusion as long as cancer does not extend beyond the area perfused by a single artery. Floxuridine, an antimetabolite and anti-neoplastic agent (0.1 to 0.6 mg/kg daily by intra-arterial infusion), is used to treat brain, breast, head, neck, liver, gallbladder, and bile duct cancer (see also Figure 15). 

Inhibition of the development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid and protein synthesis... 

Substantial inhibition of ribonucleic acid (RNA) synthesis (86% inhibition) by trichothecene myco-toxin was observed in human (HeLa) cells,47 but T-2 toxin had minor effects (15% inhibition) on RNA synthesis in Vero cells.46 The trichothecene myco-toxin-related inhibition of RNA synthesis is probably a secondary effect of the inhibition of protein synthesis. Scheduled DNA synthesis is strongly inhibited in various types of cells that are exposed to trichothecene mycotoxins. In mice or rats treated with trichothecene mycotoxins, DNA synthesis in all tissues studied was suppressed, although to a lesser degree than protein synthesis.49 The pattern by which DNA synthesis is inhibited by the trichothecene mycotoxins is consistent with the primary effect of these toxins on protein synthesis. In appropriate cell models, for the most part, trichothecene mycotoxins demonstrate neither mutagenic activity nor the capacity to damage DNA.50... 

In an early report [48], it was stated that novobiocin inhibits the synthesis of the bacterial cytoplasmic membrane, as it decreased the crypticity of E. coli strain ML 35 and caused a loss of ribonucleic acid (RNA) into the surrounding medium. These effects were not induced in resting cells and indicated that the antibiotic interfered with the synthesis of new membrane material. Another early investigation had shown that novobiocin induced the loss of 260 nm absorbing material from washed suspensions of Staph, aureus [64]. 

Azo dyes are known for their medicinal importance and are widely recognised for their use in several therapeutic areas including antineoplastics [42], antidiabetics [43], antiseptics [44], antibacterial [45] and antitumour [18]. They are known to be involved in a number of biological reactions such as the inhibition of deoxyribonucleic acid (DNA), ribonucleic acid, protein synthesis, carcinogenesis and nitrogen fixation... 

Trimethoprim and tetroxoprim inhibit folic acid synthesis, i. e., they specifically inhibit the dihydrofolate reductase which is responsible for synthesis of folic acid. They make possible the reduction of dihydrofolic acid to tetrahydrofolic acid. The structure of purines and pyrimidines is thereby interrupted, an essential step in the synthesis of proteinic and ribonucleic acid. This inhibitory effect is selective and affects bacteria only. 

The information which specifies the amino-acid sequence of a protein is stored in the nucleotide sequence of the double helix of deoxyribonucleic acid (DNA). The transcription of sections of this information into ribonucleic acid (RNA) is catalysed by RNA polymerases. These enzymes not only control the synthesis of RNA but also recognize stop and start signals on the DNA. The start signals are complex and may be blocked by repressor molecules which inhibit the transcription process. Once synthesized, the (messenger) RNA is processed and exported to ribosomes where its nucleotide sequence is translated into protein. Triplets of three nucleotides (codons) in the messenger RNA each specify (encode) one amino acid. The linear sequence of nucleotides in the messenger RNA thus specifies the sequence of amino acids in the protein whose primary structure will therefore correspond directly to the sequence of nucleotides in the DNA. 

Amanita toxins (amataxkis) are cyclic octapeptides that reduce protein synthesis by inhibiting ribonucleic acid (RN polymerase and transcription. 

Baltimore, D., Franklin, R. M. and Callender, J., 1963, Mengovirus induced inhibition of host ribonucleic acid and protein synthesis, Biochim. Biophys. Acta 76 425. 

Hunter, T., Hunt, T., Jackson, R. J., and Robertson, H. D., 1975, The characteristics of inhibition of protein synthesis by double-stranded ribonucleic acid in reticulocyte lysates, J. Biol. Chem. 250 409. 

The observation that irradiation of reassortant viruses did not impair their effect on host cell DNA synthesis extends the studies of Shaw and Cox (1973), who found that UV irradiation of reovirus did not abolish the inhibitory effect on host DNA synthesis, suggesting that either a component of the virus is capable of causing inhibition or that ribonucleic acid can function after inhibition to give rise to an inhibitory component. Possibly, an initial al protein-cell interaction could exert the inhibitory effect. Alternatively, the transcription of... 

Necrosis is often initiated by damage to membranes, either the plasma membrane of the cell or the membranes of organelles, particularly mitochondria (Zimmerman, 1999). Cell membrane damage is often caused by membrane phospholipid peroxidation. Plasma membrane damage interferes wi ion regulation, calcium homeostasis, energy production, and decrease in the ability of that organelle to sequester calcium. Inhibition of protein synthesis is an alternative mechanism that may cause cell necrosis. Toxins that act in this way include phalloidin and related mushroom toxins, which inhibit the action of ribonucleic acid (RNA) polymerase, and therefore mRNA synthesis (Pineiro-Carrero and Pineiro, 2004). 

Ennis, H. L. Protein synthesis and the inhibition of host messenger ribonucleic acid production in bacteriophage T4-infected Escherichia coli. Virology 40, 727-733 (1970). 

Kennell, D. Inhibition of host protein synthesis during infection of Escherichia coli by bacteriophage T4. I. Continued synthesis of host ribonucleic acid. J. Virol. 2, 1262-1271 (1968). 

Raghavan, V., and Tunc, H. F. (1967). Inhibition of two-dimensional growth and suppression of ribonucleic acid and protein synthesis in the gametophytes... 

A number of early observations pointed the way towards our current concepts of protein synthesis. Cells that are particularly active in protein synthesis are rich in cytoplasmic ribonucleic acid (RNA) and ribonucleoprotein (RNA-protein). Further, in a number of studies with intact cells it was found that their rate of protein synthesis varied directly as their cytoplasmic nucleic acid content and that their synthesis of protein was strongly inhibited by ribonuclease (which degrades RNA) and also by chloramphenicol. More recently, limited protein synthesis has been achieved in cell-free preparations obtained from bacterial and higher plant cells and reinforced by the addition of appropriate mixtures of the 20 protein amino acids and a suitable energy source such as ATP. Such in-vitro protein synthesis, most readily followed by studying the incorporation of C-labelled amino acids into protein, is prevented by adding ribonuclease or chloramphenicol. 

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