RNA and Protein Synthesis

Estrogens stimulate cellular proliferation, induce RNA and protein synthesis of uterine endometrium and the fibrous connective tissue framework for ovaries, and increase the size of the cells. This effect leads to the growth and regeneration of the endometrial layer and spinal arterioles, and increase in the number and size of endometrial glands. Under the influence of estrogen, vaginal mucosa becomes thicker, as cervical mucus becomes thinner (85,86). 

While the exact mechanism of action remains unclear, dacarbazine appears to inhibit DNA, RNA, and protein synthesis. Dacarbazine disappears rapidly from the plasma, with a terminal half-life of about 40 minutes. Dacarbazine has shown clinical benefit in the treatment of melanoma, Hodgkin s lymphoma, and soft tissue sarcomas. Side effects include myelosuppression, severe nausea and vomiting, and a flulike syndrome that starts about 7 days after treatment and lasts 1 to 3 weeks. 

Folic acid antagonist inhibits dihydrofolate reductase (DHFR) blocks reduction of folate to tetrahydrofolate inhibits de novo purine synthesis results in arrest of DNA, RNA, and protein synthesis... 

Piddock, L. J. V., Walters, R. N., and Diver, J. M. (1990). Correlation ofquinolone MIC and inhibition ofDNA, RNA and protein synthesis and induction of the SOS response in Escherichia coli. Antimicrob. Agents Chemother. 34, 2331-2336. 

Low concentrations (10 /iM or less) of mercury have little effect on cellular viability and stimulate RNA and DNA synthesis, whereas higher concentrations are cytotoxic and inhibit DNA, RNA and protein synthesis [145, 146, 246-248 ]. Mercuric chloride is able to selectively block CHO (Chinese hamster ovary) cells in S phase, which is related to the chemical reactivity and uptake into the cells [249], The cytotoxicity of mercury(II) compounds is probably related to their ability to inhibit DNA polymerase a activity and inhibit not only DNA synthesis but also DNA repair [250, 251]. 

Granelli-Pipemo, A., Vassalli, J.-D., Reich, E. (1979). RNA and protein synthesis in human peripheral blood polymorphonuclear leukocytes. J. Exp. Med. 149, 284-9. 

As a matter of fact, cosolvents such as primary alcohols, polyols, di-methylformamide and dimethyl sulfoxide are now almost routinely used to perturb the overall reactions and elementary equilibria or rate processes of the highly organized systems carrying out DNA, RNA, and protein synthesis. However, in spite of the fact that such systems respond well and in a reversible way to these perturbations, cosolvent effects remain relatively poor probes of reaction mechanisms (Hamel, 1972 Voigt et al., 1974 Ballesta and Vasquez, 1973 Crepin et ai, 1975 Nakanishi et al., 1974 Brody and Leautey, 1973). The most common result reported upon addition of increasing amounts of cosolvents is a bell-shaped curve equilibria and rate processes are first stimulated and... 

Bleomycin is a complex of no less than 16 glycopeptide antibiotics made from the family Streptomyces verticilus, which have different R groups [88-94]. Bleomycines exhibit antitumor, antiviral, and antibacterial activity. When bound to DNA, they disturb the spiraling of both single and double strands of DNA. To a lesser degree, they inhibit RNA and protein synthesis. It is administered both intravenously and intramuscularly. 

Pharmacology Trimetrexate, a 2.4-diaminoquinazoline, nonclassical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death. Pharmacokinetics Clearance was 38 15 ml /min/m and volume of distribution at steady state (Vdgs) was 20 8 L/m. The plasma concentration time profile declined... 

The antitumor activities of indole and isatin oximes and of furan oximes were studied by several investigators. Furan oximes were found to inhibit DNA, RNA and protein synthesis in lipoid leukemia cells. Derivatives of quinoline oximes were also shown to possess antitumor activity , and glucosinolates, 15, were suggested as cancer-preventive agents . ... 

The level of EPO production in the kidneys (or liver) is primarily regulated by the oxygen demand of the producer cells, relative to their oxygen supply. Under normal conditions, when the producer cells are supplied with adequate oxygen via the blood, EPO (or EPO mRNA) levels are barely detectable. However, the onset of hypoxia (a deficiency of oxygen in the tissues) results in a very rapid increase of EPO mRNA in producer cells. This is followed within 2 h by an increase in serum EPO levels. This process is prevented by inhibitors of RNA and protein synthesis, indicating that EPO is not stored in producer cells, but synthesized de novo when required. 

Some drugs that exert their maximum cytotoxicity during the S-phase of the cycle also prevent cells from progressing through the cell cycle to the S-phase this is accomplished by sublethal inhibition of RNA and protein synthesis. The antimetabolites methotrexate, fluo-rouracU, and mercaptopurine all can inhibit RNA synthesis in Gi- and Gz-phases and inhibit DNA synthesis during S-phase. This inhibition of cell cycle progression actually may result in reduced cytotoxicity, and such agents have been termed S-phase-specific but self-limited. 

Cells in S-phase are most sensitive to the cytotoxic effects of methotrexate. RNA and protein synthesis also may be inhibited to some extent and may delay progression through the cell cycle, particularly from Gj to S. 

Mechanism of Action An antifungal that penetrates fungal cells and is converted to fluorouracil which competes with uracil interfering with fungal RNA and protein synthesis. Therapeutic Effect Damages fungal membrane. 

Mechanism of Action An antimetabolite that competes with enzymes necessary to reduce folic acid to tetrahydrofolic acid, a component essential to DNA, RNA, and protein synthesis. This action inhibits DNA, RNA, and protein synthesis. Therapeutic Effect Causes death of cancer cells. 

It acts by inhibiting dihydrofolate reductase. It inhibits conversion of dihydrofolic acid to tetrahydrofolic which is essential for purine synthesis and amino acid interconversions. It primarily affects DNA synthesis but also RNA and protein synthesis. It has cell cycle specific action and kills cells in S phase. It is readily absorbed from gastrointestinal tract but larger doses are absorbed incompletely, little drug is metabolised and it is excreted largely unchanged in urine. 

The p53 protein is at the center of apoptotic signaling pathways initiated by DNA damage and defects in the course of the cell cycle. Depending on cell type, p53-induced apoptosis either requires transcriptional activation (Polyak et al., 1997) or occurs without new RNA and protein synthesis (see Fig. 14.10). 

Proposed mechanism of action of daptomycin. Daptomycin first binds to the cytoplasmic membrane (step 1) and then forms complexes in a calcium-dependent manner (steps 2 and 3). Complex formation causes a rapid loss of cellular potassium, possibly by pore formation, and membrane depolarization. This is followed by arrest of DNA, RNA, and protein synthesis resulting in cell death. Cell lysis does not occur. 

A number of biochemical events have been found to occur. RNA and protein synthesis are inhibited, and membrane damage can be observed two hours after dosing. There is also an increase in intracellular calcium, which may be the crucial event that leads to cell death... 

A thorough investigation12 of the effects of the unsaturated ketonu-cleoside 61a on KB cells in culture confirmed the high cytotoxic potency of this compound. Moreover, it appeared that, at low doses, where no cytotoxic effect occurs, the ketonucleoside impaired DNA, RNA, and protein synthesis, and strongly inhibited cell multiplication. 

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