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PubMed1982

Effect of cycloheximide on deciduoma morphogenesis and implantation in rats.

Intraperitoneal administration of cycloheximide (1 mg/kg body weight) to rats immediately after an artificial deciduoma induction inhibits the development of decidual tissue. Besides inhibiting the differentiation of stromal to decidual cells, wet weight and levels of uterine protein and RNA are low following the antibiotic treatment. Injection of the drug (1 mg/kg body weight) into pregnant rats, either on the eve of Day 4 or in the morning of Day 5 of pregnancy, does not prevent implantation but interferes with the growth of embryos.

Animals↗
PubMed1983

The role of glucose and aminoacid starvation in the sensitivity of protein and RNA synthesis to cycloheximide and erythromycin in the yeast Saccharomyces cerevisiae.

In Saccharomyces cerevisiae dependence of ribonucleic acid synthesis on protein synthesis occurring during nutritional shift down conditions was evidenced. The results obtained indicated that yeast had "stringent control" of ribonucleic acid synthesis and that this control was reversed by cycloheximide only under glucose starvation or ammonia starvation in the presence of acetate as carbon source (phenotypic relaxation). Therefore, it appeared that the "phenotypic relaxation" of RNA synthesis depended on the carbon source present in the medium suggesting that the process could be negatively controlled by glucose or by some glucose catabolite(s). Such a phenotypic relaxation was sensitive to erythromycin treatment. On the other hand, total protein synthesis carried out during amino-acid starvation in the presence of glucose or ammonia starvation in the presence of acetate was 30%-40% inhibited by erythromycin, showing that in these conditions sensitivity to a non legitimate inhibitor could be triggered off in an haploid strain, and that such sensitivity did not depend on the presence of glucose in the medium.

Amino Acids↗
PubMed1983

Use of cycloheximide for cultivating Mycobacterium lepraemurium in cell culture.

A serial increase in the number of Mycobacterium lepraemurium with successful subcultures has been obtained in cell culture with cycloheximide treatment. The infected cells seldom floated off the culture vessel. They could be maintained and would support the bacillary multiplication in good condition for ten weeks or more without changing the medium frequently. An overall generation time of the intracellular bacilli up to the tertiary culture for the total period of 35 weeks was 22.1 days.

Cells, Cultured↗
PubMed1983

Effects of cortisone, cytochalasin B and cycloheximide on strains of Chlamydia psittaci in cell cultures.

Vero and McCoy cell cultures were tested for their susceptibility to Chlamydia psittaci in the presence of several antimetabolites, such as cortisone acetate, cytochalasin B and cycloheximide. Vero cells were more susceptible than the McCoy cell cultures as demonstrated by cytopathic changes, fluorescent antibody activity, and titer of C. psittaci. Although all of the antimetabolites increased these parameters, a mixture of cortisone and cytochalasin B was the most effective.

Animals↗
PubMedDate not supplied

[Synthesis and phosphorylation of histones and nonhistone proteins as affected by irradiation and serotonin in cycloheximide-synchronized hepatocytes].

Phosphorylation and synthesis of histones and nonhistone proteins were studied after the inhibition of translation by sublethal cycloheximide doses. Activation of the chromatin protein phosphorylation was noted: (1) at the stage of recovery and stimulation of the protein synthesis (18-24 h), and (2) at the stage of activation of the replicative DNA synthesis (30-60 h). Phosphorylation and synthesis of the chromatin proteins depended upon the individual or combined effect of X-radiation and serotonin. The authors discuss the possible role of the chromatin protein phosphorylation in the response of the nuclear apparatus to the effect of radiation and serotonin the latter being used as a radioprotective agent.

Animals↗
PubMedDate not supplied

[Effect of cycloheximide and actinomycin D on the phospholipid and neutral lipid content of Cunninghamella japonica].

Changes in the composition of neutral lipids and phospholipids were studied during the growth of Cunninghamella japonica under the action of cycloheximide and actinomycin D. The data were used to discuss how the synthesis of enzymes catalysing the formation of individual lipid classes was regulated and whether it would be possible to control the composition of phospholipids and neutral lipids using inhibitors of RNA and protein synthesis. The results are also indicative of a certain correlation between growth phases of the fungus and changes in certain characteristics of membrane lipids.

Cycloheximide↗
PubMed1984

[Relation of the biosynthesis of intracellular and export proteins in rat liver cells during induction of proliferation by cycloheximide].

After a single injection of a sublethal dose of cycloheximide (CHI) the biosynthesis of extracellular proteins in rat hepatocytes was rapidly suppressed, the reconstitution being very slow. On the contrast, the biosynthesis of intracellular proteins (e.g., histones, and other acid-soluble liver proteins) was more resistant to CHI. The activation of biosynthesis of acid-soluble and acid-insoluble proteins was found to occur stepwise. It was assumed that the activation of synthesis and accumulation of intracellular proteins after CHI release accompanied by a decreased synthesis of extracellular proteins is one of possible causes of stimulation of DNA synthesis in the hepatocytes following a single injection of CHI.

Animals↗
PubMed1978

Effect of cycloheximide on the bone marrow toxicity of nitrogen mustard.

Cycloheximide (CHM), a potent inhibitor of protein synthesis, has been reported to protect rat intestinal crypt cells from mitotic inhibition by nitrogen mustard (HN2). For investigation of the effect of CHM on the bone marrow toxicity of HN2, CHM (1.0 mg/kg) and HN2 in doses up to 2.5 mg/kg were given i.p. to rats. Twenty-eight % (13 of 46) of rats given HN2 alone died within 5 days. Only 4% (2 of 45) of rats pretreated with CHM died within 5 days after the administration of HN2. Rats pretreated with CHM had significantly less leukopenia and granulocytopenia than did rats given HN2 alone, and their bone marrow cellularity, assessed by histological sections and total femoral marrow cell counts, was greater than that of animals given HN2 alone. Bone marrow DNA synthesis, as measured by in vitro [3H]thymidine incorporation, was decreased 2 hr after HN2 injection, appeared to recover at 4 hr, but was further decreased at 24 and 48 hr. CHM given up to 20 min before HN2 reversed the effect of HN2 on DNA synthesis at 2 and 4 hr. A variable protective effect of CHM was observed at 24 and 48 hr. These studies indicate that CHM increases the survival of HN2-treated rats and partially protects rat bone marrow cells from HN2 cytotoxicity.

Animals↗
PubMed1978

[Effects of cycloheximide and chlorotetracycline on the activities of RNA-polymerases in mouse liver nuclei].

The activities of RNA-polymerases I and II in mouse liver nuclei isolated after injection of various poisons to mice were studied. An increased activity of RNA-polymerase I in the nuclei isolated from mouse liver after injection of the inhibitors of translation, i.e. cycloheximide and chlorotetracycline, was found. The activity of RNA-polymerase II remained unchanged. The inhibition of protein synthesis in mitochondria following the injection of chloramphenicol did not affect the activities of nuclear RNA-polymerases. The animal poisoning by carbon tetrachloride accompanied by a total decrease of the rates of protein and RNA synthesis in the liver decreased the activities of both RNA-polymerases, the activity of RNA-polymerase II being inhibited stronger as compared to that of RNA-polymerase I.

Animals↗
PubMed1978

Stimulation of prostaglandin synthesis by tumor-promoting phorbol-12, 13-diesters in canine kidney (MDCK) cells. Cycloheximide inhibits the stimulated prostaglandin synthesis, deacylation of lipids, and morphological changes.

Tumor-promoting 12-O-tetradecanoyl-phorbol-13-acetate and phorbol-12, 13-di-decanoate, but not the non-tumor-promoting 4alpha-phorbol-12, 13-di-decanoate, stimulated deacylation of cellular lipids, prostaglandin biosynthesis, and morphological changes in cultured MDCK cells. The increased prostaglandin biosynthesis and morphological changes required at least 24 h for expression. Cycloheximide inhibited the stimulated prostaglandin biosynthesis, the changes in morphology, and the increased lipid deacylation, but hydrocortisone (1.0 microgram/ml) did not. Indomethacin (0.5 microgram/ml) completely inhibited the stimulated prostaglandin biosynthesis and also inhibited some deacylation of cellular lipids. Indomethacin, however, did not effect the 12-O-tetradecanoyl-phorbol-13-acetate-stimulated changes in morphology.

Cell Line↗
PubMed1983

Effect of cycloheximide on skin and renal radiation tolerance in the rat.

The effect of cycloheximide (CHM) on skin and renal radiation tolerance in the rat has been studied. When administered 24 hr prior to a range of single radiation doses to the hind limbs, the drug protected against skin damage. When administered at intervals of 45 min to 100 hr prior to single-dose irradiation of the kidneys, no protection against renal injury, as manifested by blood pressure, urine creatinine level, and lethality, was observed. CHM-induced alteration in the cell cycle may confer radioprotection to a rapidly proliferating cell renewal system such as the skin and exert no radioprotective action in slowly proliferative tissue such as kidney.

Animals↗
PubMed1984

[Sequential activation of various types of nuclear RNA polymerases of rat liver cells during the process of DNA synthesis induction by cycloheximide].

The dynamics of changes in the activity of RNA polymerases I and II (EC 2.7.7.6) and the activities of free and bound forms of RNA polymerase II in isolated rat liver nuclei after a singular injection of sublethal dose of cycloheximide (CHI) was studied. Activation of RNA polymerases occurs in three steps. The first step (1--2 hours after CHI injection) coincides with inhibition of protein synthesis and predominant activation of both forms of RNA polymerase II. The second step (6--24 hours after CHI injection) is characterized by de novo protein synthesis and activation of RNA polymerase I and RNA polymerase II. The third step (36--48 hours after CHI injection) witnesses activation of both RNA polymerases which coincides with the beginning of stimulation of DNA replication. It is assumed that this step is coupled with the synthesis of a special form of RNA polymerase, RNA polymerase IV, which is responsible for transcription of genes synthesizing various chromatin components (histones, NHB, RNA prime). At all steps the activity of free RNA polymerase II remains at a sufficiently high level. Consequently, the activity of chromatin is limited by chromatin structure rather than by RNA polymerase II content in it. Presumably, such activation of various forms of RNA polymerase is essential for cell preparation for DNA replication.

Animals↗
PubMed1984

Organ culture of fetal rat intestine. Effects on brush border enzyme activities of the combined administration of dexamethasone and cycloheximide or actinomycin D.

Jejunum of 19-day fetal rats was explanted in organ culture for 48 h in the presence of dexamethasone (DX) and cycloheximide (CX) or actinomycin D (Act D). The concentrations of both inhibitors which provided maximal responses without any detrimental alteration of the tissue were determined. During the culture period, CX (0.5 microgram/ml) totally abolished the production of both DX-stimulated enzymes (sucrase, maltase, lactase) and DX-insensitive enzymes (aminopeptidase, alkaline phosphatase). On the contrary, Act D at 2 micrograms/ml exhibited differential levels of inhibition related to the enzyme considered: 100% for sucrase and aminopeptidase, 70% for maltase and 50% for lactase. By contrast, alkaline phosphatase was stimulated 100% by Act D. These data suggest that the mechanism by which DX induces sucrase and stimulates maltase activity takes place at the transcriptional level. They also indicate that the basic maturation of at least maltase and lactase activities depends upon the traduction of a preexisting pool of mRNAs. The superinduced alkaline phosphatase activity obtained with Act D supports the notion that an Act D-sensitive repressor may play a role in the maturation process of this enzyme.

Animals↗
PubMed1982

The phosphorylation of ribosomal protein S6 in rat tissues following cycloheximide injection, in diabetes, and after denervation of diaphragm. A simple immunological determination of the extent of S6 phosphorylation on protein blots.

The extent of phosphorylation of S6 was measured in a variety of cells, organs, and tissues using a simplified procedure. Ribosomal proteins were separated by electrophoresis on a one-dimensional urea-sodium dodecyl sulfate gel. They were transferred electrophoretically to nitrocellulose, and S6 was specifically stained by means of its reaction with a monoclonal antibody. The mobility of the stained protein was shown to be a measure of the extent of its phosphorylation. Using this method, we found that cycloheximide injection of rats gives rise to the phosphorylation of S6 in a variety of organs and tissues: diaphragm, heart and skeletal muscle liver and kidney, but not brain. Diabetes induced with alloxan did not result in the phosphorylation of S6 in any of the tissues examined, and subsequent insulin injection resulted in a slight increase in the phosphorylation of S6 in liver. Insulin injection in normal rats also caused the phosphorylation of liver S6. Unilateral denervation of rat diaphragm resulted in phosphorylation of S6 in the denervated portion but not in the innervated portion of the diaphragm.

Animals↗
PubMed1981

[Intestinal lymphatic absorption of labelled oleic acid in the normal rat and rat treated with actidione-cycloheximide or acetoxycycloheximide].

Actidione-cycloheximide or acetoxycycloheximide treated and control Rats prepared with main mesenteric lymph duct cannulation were infused with a 90 mumol lipid emulsion composed of an equimolar mixture of monopalmitin, palmitic acid and 14C oleic acid and added with bile. In control Rats 75% of 14C oleic was recovered in lymph instead of 4,5% in treated rats. Although a low amount of lipids was concerned in this experiment, actidionecycloheximide and acetoxycycloheximide strongly inhibit intestinal absorption of oleic acid in lymph.

Animals↗
PubMedDate not supplied

[DNA synthesis in the liver of irradiated and serotonin-protected rats after removal of the cycloheximide block].

The cycloheximide block model was proposed to study the mechanism of action of both radiation and radioprotectors. It was shown that irradiation of proliferating hepatocytes in vivo, at early stages of the prereplicative phase, markedly inhibited DNA synthesis. Serotonin, in its turn, considerably increased DNA synthesis maintaining this increase after subsequent exposure to X-radiation.

Animals↗
PubMed1978

[Effect of cycloheximide on DNA replication. III. Results of autoradiography of the DNA of lysed cells].

With the help of DNA-fiber autoradiography on L cells, the question of mechanism of a rapid block of DNA replication by cycloheximide, an inhibitor of protein synthesis, was examined. The presented data show that the elongation of labeled regions in replicating units is blocked. In non-treated cells the replication rate was 0.4 mcm/min; the mean size of replicon was 21 mcm. The difficulties encountered in the explanation of the data obtained are discussed.

Autoradiography↗
PubMed1982

[Replicative methylation of DNA in L-cells: effect of S-isobutyladenosine and cycloheximide and possible existence of two DNA-methylases].

Methylation of DNA in cultured cells of mouse fibroblasts (L-cells) occurs at least in two steps, i. e. methylation of Okazaki fragments (up to 100 . m5C/C + m5C = 2.8-2.9) and methylation of linkage sites of DNA formed by ligation of the fragments (up to 6.0). The synthesized Okazaki fragments are not subjected to further methylation, since about one half of their methylation sites (CG) remains non-modified. The transmethylation inhibitor S-isobutyladenosine (SiBA) inhibits the methylation of the "linkage" sites of the newly synthesized DNA without affecting that of the Okazaki fragments. The repression of protein synthesis (including that of histones) by cycloheximide in the course of replication reveals some additional methylation sites. The level of methylation of the newly synthesized polymeric DNA reaches thereby 6.0, which corresponds to modification of all its CG-dinucleotides. A model for replicative methylation of DNA based on the existence of two DNA-methylases differing in their specificity is proposed. It is assumed that one of the DNA methylases is highly specific and functions within the complex with DNA-polymerase, while the other possesses a restricted specificity and functions in a free form (i. e. apart from the replicative complex).

Animals↗