Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cycloheximide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1984

Cycloheximide-sensitive recovery from 254 nm UV light damage in cultured marsupial cells.

Colony-forming ability of Potorous tridactylus-kidney (PtK-2) cells was measured after exposure to 254-nm ultraviolet (UV) light and cycloheximide. Addition of 5 microM cycloheximide after exposure of the cells to UV light greatly decreased cell survival. Maximum effect of the drug was obtained by 24-h exposure after irradiation. The cycloheximide sensitivity of irradiated cells was eliminated if addition of the drug was delayed for 8-10 h after irradiation, or if the cells received photoreactivating light treatment prior to cycloheximide exposure. Thus, a major component of pyrimidine dimer removal may involve a cycloheximide-sensitive mechanism.

Animals↗
PubMed1991

Cycloheximide genotoxicity in in vitro and in vivo test systems.

The aim of this study was to investigate if there was any genotoxic effect produced by the antibiotic cycloheximide, widely used as a fungicide in agriculture as well as in everyday laboratory practice. The battery of test systems included the bacterium Salmonella typhimurium (strains TA98 and TA100), the yeast Saccharomyces cerevisiae (D7), Allium cepa somatic cells and mouse bone marrow cells. This combination of test systems enabled us to establish possible effects caused by cycloheximide at different levels of the genome and to indicate a possible mechanism of action. The results obtained in experiments showed that cycloheximide did not induce frameshift or base-pair substitution mutations in S. typhimurium regardless of metabolic activation. In S. cerevisiae cycloheximide had only toxic effects but no increase of mitotic gene conversion was noticed under the conditions of the experiment. However, in A. cepa somatic cells as well as in mouse bone marrow cells cycloheximide showed its activity causing different genetic damages, e.g., chromosome breaks, mitotic disturbances and nuclear abnormalities.

Allium↗
PubMed1984

Dual action of cycloheximide on memory formation in day-old chicks.

Amnesia for a single trial discriminated passive avoidance learning task in day-old chicks, resulting from the antibiotic cycloheximide, is shown to begin after 30 min following learning when cycloheximide is given immediately after or before learning. However, amnesia does not begin until after 50 min following learning when cycloheximide is given 5 min or later after learning. The results are interpreted in the context of a 3 stage model of memory formation. It is suggested that the second or intermediate stage involves two phases: phase A which lasts up to 30 min following learning, is energy dependent, and is susceptible to inhibition by 2,4-dinitrophenol; phase B which occurs after phase A, lasts up to 50 min following learning, is energy independent, and is not susceptible to inhibition by 2,4-dinitrophenol. It is concluded that cycloheximide given immediately after or before learning inhibits expression of phase B of intermediate memory as well as formation of long-term memory, while cycloheximide given 5 min or later after learning only inhibits formation of long-term memory. Another antibiotic, anisomycin, is shown to have no effect on intermediate memory, independent of time of administration.

2,4-Dinitrophenol↗
PubMed1989

Dexamethasone control of growth hormone mRNA levels in GH3 pituitary cells is cycloheximide-sensitive and primarily posttranscriptional.

To clarify the mechanism of growth hormone (GH) gene activation by glucocorticoids in GH3 pituitary cells, GH mRNA accumulation in nuclear and cytoplasmic compartments was measured in the presence and absence of cycloheximide. In dexamethasone-treated cells, levels of GH mRNA were increased in the nucleus by 6 h and in the cytoplasm by 12 h. Dexamethasone treatment caused a 5- to 24-fold rise in total GH mRNA levels by 48-72 h. The differential elevation of nuclear levels of GH mRNA relative to the amount of cytoplasmic GH mRNA persisted for 48 h. A transient accumulation of GH mRNA in the nucleus was followed by a brief rise in cytoplasmic GH mRNA levels in GH3 cells treated simultaneously with dexamethasone and cycloheximide. In GH3 cells pretreated for 2 h with cycloheximide, the rise in nuclear and cytoplasmic GH mRNA levels mediated by dexamethasone was blocked completely. Levels of glucocorticoid receptor were unaffected by cycloheximide. These data suggest that the stimulation of GH mRNA levels by glucocorticoids is initiated within the nucleus and that cycloheximide-sensitive events are essential for this stimulation to occur. To assess the importance of GH gene transcriptional activation by glucocorticoids, nuclear transcription run-on reactions and assays of GH promoter activity in an aminoglycoside 3'-phosphotransferase (Neo) fusion gene within stably transformed GH3 cells were performed. Evidence for a weak, transient transcriptional activation of the GH gene by dexamethasone in nuclear run-on assays was obtained. Consistent with this idea, a 30-72 h exposure to dexamethasone raised levels of Neo mRNA in GH-Neo GH3 cell transformants by less than or equal to 2-fold. We conclude that glucocorticoid stimulation of GH mRNA in GH3 cells requires ongoing protein synthesis and can occur largely independently of GH gene transcriptional activation.

Animals↗
PubMed1976

Effects of cycloheximide on protein degradation and gluconeogenesis in the perfused rat liver.

Cycloheximide at concentrations above 18 muM produced a 93% inhibition of total protein synthesis measured by valine incorporation in the perfused rat liver. Rates of protein degradation were estimated by perfusing livers prelabeled in vivo with L-[1-14C]valine with medium containing 15 mM L-valine. Thus labeled valine released from liver protein during perfusion was greatly diluted and reincorporation of label was minimized. Cycloheximide at 18 muM inhibited protein degradation by over 60%, after a delay of 15-20 min. Associated with these effects were dose-dependent increases in the rates of glucose and urea production. Glucose production increased 3 fold, from 0.54 +/- 0.07 in control to 1.85 +/- 0.24 mumol/min/100 g rat in cycloheximide-treated livers. Urea production increased from 0.24 +/- 0.02 to 0.62 +/- 0.06 mumol/min/100 g rat. No changes in liver glycogen or cyclic AMP content were seen. The data suggest that inhibition of protein synthesis provides an increased availability of intra-cellular amino acids and that many of these are rapidly degraded, yielding urea and glucose. This is supported by the fact that intracellular alanine levels were significantly increased following cycloheximide treatment. It is possible that the inhibition of protein degradation by cycloheximide is due to altered intra-cellular pools of amino acids or their metabolites.

Amino Acids↗
PubMed1976

The effect of cycloheximide on galactosyltransferase of rat liver Golgi membranes.

An inhibitory effect of cycloheximide on the initial rate of galactosyltransferase of rat liver Golgi membranes has been demonstrated. Cycloheximide was effective in inhibiting the activity of the enzyme when added directly to the assay medium or after pre-incubation of the membranes with the drug. The inhibition observed with different concentrations of nucleotide sugar was shown to be competitive at higher concentrations of the nucleotide sugar (0.10-1.0 mumol). The inhibition observed with different concentrations of acceptor, N-acetylglucosamine was complex and could not be analysed further with the present data. Washing the Golgi membranes previously incubated with cycloheximide with water failed to reverse the inhibition. Washing with UDPgalactose partially reversed the inhibition only. These results, together with the observation that serum galactosyltransferase was not inhibited by cycloheximide supported the view that the cycloheximide effect may be primarily on the membrane system.

Acetylglucosamine↗
PubMed1981

Density labelling characterisation of the effects of cordycepin and cycloheximide on the turnover of phenylalanine ammonia-lyase.

L-Phenylalanine ammonia-lyase (EC 4.3.1.5) undergoes a transient increase in activity in illuminated disc of Solanum tuberosum tuber parenchyme. Cycloheximide and cordycepin inhibit the initial increase in enzyme activity, but if addition of these anti-metabolites is delayed until the time of maximum enzyme levels, the subsequent decline in enzyme activity is inhibited (Lamb, C.J. (1977) Planta, 135, 169-175). The effect of delayed treatment with cycloheximide or cordycepin on the turnover of phenylalanine ammonia-lyase has been analysed by density labelling with 2H from 2H2O. Delayed introduction of cycloheximide or cordycepin reduces the rate of labelling of phenylalanine ammonia-lyase whilst preventing the decay in enzyme activity observed in controls not treated with inhibitor, and this labelling pattern cannot be accounted for by effects of cycloheximide or cordecypin on the labelling of amino acid pools. It is concluded that delayed treatment with cycloheximide or cordycepin leads to the maintenance of high levels of phenylalanine ammonia-lyase by inhibition of the removal of active enzyme rather than by maintenance of high rates of enzyme synthesis.

Ammonia-Lyases↗
PubMed1996

Critical period for cycloheximide blockade of light-induced phase advances of the circadian locomotor activity rhythm in golden hamsters.

Recent studies indicate that the protein products of genes involved in transcriptional regulation play an important role in light-induced phase-shifting of the circadian clock, and suggest that protein synthesis may be necessary for some critical steps in the process by which light can induce a phase shift. In order to determine if this protein-dependent step occurs before, during or at some time after the light pulse is presented, golden hamsters were treated with the protein synthesis inhibitor, cycloheximide (65 mg/kg, injected subcutaneously), at various times relative to the presentation of a light pulse that normally induces an advance in the circadian locomotor activity rhythm. When hamsters were treated with cycloheximide 1 h or 30 min before, as well as 0, 1, 2, 3 or 4 h after the onset of the light pulse; the phase advancing effects of light were completely blocked and delay phase shifts were observed. The observed phase shifts in these groups of animals were not significantly different from those observed in animals treated with cycloheximide without exposure to light. Treatment with cycloheximide 6 or 3 h before the light pulse partially blocked light-induced phase advances. The phase advancing effects of light were not altered in those animals injected with cycloheximide 6 or 9 h after the light pulse. These results support the hypothesis that protein synthesis is necessary for light-induced phase advances in the mammalian circadian clock, and indicate that such synthesis is necessary for at least 4 h after the light pulse for phase shifts to occur. Thus, light may not induce an instantaneous (< 1 h) phase shift in the circadian clock of hamsters, but instead depends on the synthesis of proteins for about 4 h after light stimulation.

Animals↗
PubMed2002

Non-linear effects of cycloheximide in glutamate-treated cultured rat cerebellar neurons.

Multiple cell types and organisms across a wide array of phyla and a variety of toxins demonstrate non-linear dose responses to low-level chemical exposures with high doses inhibiting cellular function and low doses stimulating function. We tested whether such non-linear responses to low and ultra-low dose N-methyl-D-aspartate (NMDA), 1-methyl-4-phenylpyridinium (MPP+) or cycloheximide moderated toxic glutamate exposure in cultured cerebellar granule cells. Neurons were incubated over 72 h with successive NMDA, MPP+ iodide or cycloheximide additions producing specified low (10(-5), 10(-7), 10(-9), 10(-11), and 10(-13) M) and ultra-low (10(-27),10(-29), 10(-63), and 10(-65) M) concentrations. Subsequently these neuronal cells were exposed to a 50% excitotoxic concentration of glutamate for 24 h. Neuronal viability was significantly reduced in neurons treated with micromolar (10(-5) M) cycloheximide whereas viability was enhanced in neurons treated with an ultra-low dose exposure of 10(-27) M cycloheximide. Neither NMDA nor MPP+ elicited harmful or protective responses. This is the first report demonstrating non-linear dose-response effects of cycloheximide in low and ultra-low concentration ranges.

Animals↗
PubMed1997

Inhibition of glutathione synthesis can enhance cycloheximide-induced protection of developing neurons against axotomy.

Developing neurons depend for survival on target-derived trophic substances. These are thought to block the expression of a genetic program of cell death. Nevertheless, it is known that less orderly events such as oxidative stress are involved in neuron death. In vivo, retinal ganglion cell death induced by axotomy can be reduced by antioxidants. In this study, we investigated the effects of inhibiting glutathione synthesis by means of buthionine sulfoximine to characterize the influence of endogenous glutathione-dependent antioxidant systems on ganglion cell death. Moreover, since protein synthesis inhibition by cycloheximide has been shown to enhance glutathione synthesis in vitro, we studied the effects on cell death of intraocular injections of buthionine sulfoximine, cycloheximide and combinations of the two inhibitors. Cycloheximide's protective action did not seem to involve an increase in glutathione synthesis. Surprisingly, buthionine sulfoximine injected before cycloheximide enhanced its protective effects, whereas it inhibited them when injected later. We interpret our results as an interaction between death-promoting effects of glutathione depletion through an elevation of free radical concentrations and cycloheximide-sensitive effects of oxidative stress through the synthesis of both death-inhibiting and death-promoting proteins.

Animals↗
PubMedDate not supplied

Effect of cycloheximide on temperature regulation in rats.

The effect of cycloheximide, an inhibitor of protein synthesis, on temperature regulation in afebrile rats was studied to determine whether its reported antipyretic effect might be attributable to a non-specific antimetabolic effect. Within 60 min after administration of cycloheximide (5 mg/kg IP) to female rats at ambient temperatures of 34, 25 and 15 degrees C, a significant decrease in colonic temperature was observed as compared with control rats administered saline IP. Measurements of rate of oxygen consumption showed that cycloheximide (5 mg/kg IP) significantly depressed the ability of rats to increase their heat production during a cold stress (15 degrees C). In the cold the rate of oxygen consumption increased 8.7 +/- 0.8 ml/min/kg0.75 in the control rats but only 1.8 +/- 0.9 ml/min/kg0.75 in the cycloheximide-treated rats. Since the thermoregulatory changes accompanying cold stress are similar to those observed during the genesis of fever, these data suggest that cycloheximide may have a general depressant effect on heat production rather than a specific antipyretic effect.

Animals↗
PubMed2000

Activation of pig oocytes using calcium ionophore: effect of protein synthesis inhibitor cycloheximide.

In vitro matured pig oocytes were activated using a combined treatment of calcium ionophore A 23187 with cycloheximide. The oocytes were exposed to ionophore (10, 25 or 50 microM) for 0.5, 1, 3, 5 or 7 min and then cultured with cycloheximide (0 or 10 microg/ml) for 6 h. Cycloheximide treatment significantly increased the activation rate of oocytes and the percentage of oocytes that were able to develop after activation. The highest activation rate was observed after treatment with 50 microM ionophore. The highest percentage of developing eggs was observed after combined treatment of ionophore (25 microM) with cycloheximide. The percentage of oocytes developing up to the morula and blastocyst stage was not significantly increased after cycloheximide treatment.

Animals↗
PubMed1981

Effects of adrenocorticotropin and cycloheximide on adrenal diglyceride kinase.

We studied the effects of adrenocorticotropin (ACTH) and cycloheximide on adrenal enzymes involved in phosphatidate synthesis. Treatment of rats in vivo with ACTH induced a rapid increase in phosphatide synthesis from diglyceride and ATP in adrenal homogenates, and cycloheximide treatment prevented this increase if given before ACTH and rapidly reversed the increase if given after ACTH. The stimulatory effect of ACTH appeared to be largely due to an increase in diglyceride substrate, as kinase activity was not altered. The inhibitory effect of cycloheximide, on the other hand, appeared to be due to a decrease in diglyceride kinase activity. Neither ACTH nor cycloheximide treatment had any effect on the activity of glycerol-3'-phosphate acyltransferase or phosphatidate phosphatase. Our findings suggest that (a) ACTH increases the flow of phospholipid (and their levels) throughout the entire circular pathway, i.e., phosphatidate leads to CDP-diacylglycerol leads to inositides leads to diglycerides leads to phosphatidate, and (b) a labile protein may serve to allow entry into a recycling of diglyceride in this pathway. In addition, since cycloheximide blocked carbachol-induced increases in pancreatic and salivary glandular phosphatidate synthesis resulting from phosphatidylinositol hydrolysis and consequent diglyceride generation, the putative labile protein may have widespread importance.

Adrenal Glands↗
PubMed1999

Synthesis and cytotoxic evaluation of cycloheximide derivatives as potential inhibitors of FKBP12 with neuroregenerative properties.

On the basis of the new finding that the protein synthesis inhibitor cycloheximide (1, 4-[2-(3, 5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]-2,6-piperidinedione) is able to competitively inhibit hFKBP12 (K(i) = 3.4 microM) and homologous enzymes, a series of derivatives has been synthesized. The effect of the compounds on the activity of hFKBP12 and their cytotoxicity against eukaryotic cell lines (mouse L-929 fibroblasts, K-562 leukemic cells) were determined. As a result, several less toxic or nontoxic cycloheximide derivatives were identified by N-substitution of the glutarimide moiety and exhibit IC(50) values in the range of 22.0-4.4 microM for inhibition of hFKBP12. Among these compounds cycloheximide-N-(ethyl ethanoate) (10, K(i) = 4.1 microM), which exerted FKBP12 inhibition to an extent comparable to that of cycloheximide (1), was found to cause an approximately 1000-fold weaker inhibitory effect on eukaryotic protein synthesis (IC(50) = 115 microM). Cycloheximide-N-(ethyl ethanoate) (10) was able to significantly speed nerve regeneration in a rat sciatic nerve neurotomy model at dosages of 30 mg/kg.

Animals↗
PubMed2001

Induction of P-glycoprotein mRNA transcripts by cycloheximide in animal tissues: evidence that class I Pgp is transcriptionally regulated whereas class II Pgp is post-transcriptionally regulated.

P-glycoprotein (Pgp) are a small family of plasma membrane proteins capable of transporting substrates across cell membranes. Class I and class II Pgp are able to transport drugs and have been shown to mediate multidrug resistance (MDR). Class III Pgp is a long chain phospholipid transporter and does not mediate MDR. The expression and regulation of Pgp genes in animal tissues are not well understood. In this study, the protein synthesis inhibitor cycloheximide was used as a tool to understand Pgp gene expression and regulation in animal tissues. The sensitive RNase protection assay was used to detect changes in Pgp mRNA levels and nuclear run-on assay was used to determine whether transcription or post-transcription is important. The results showed that cycloheximide significantly induced class II Pgp expression in all tissues examined. This was predominantly through post-transcriptional effect. In contrast, the relatively modest increase in class I Pgp expression by cycloheximide was found to be mainly due to increased transcriptional activity. On the other hand, cycloheximide induced class III Pgp expression in some tissues while caused decay of class III Pgp mRNA in other tissues. The transcriptional and post-transcriptional mechanisms exerted by cycloheximide on Pgp genes are discussed. These findings have implications for our understanding of gene regulation in animal tissues and MDR reversal strategies in vivo.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1966

Ribonucleic acid synthesis in yeast. The effect of cycloheximide on the synthesis of ribonucleic acid in Saccharomyces carlsbergensis.

1. Cycloheximide causes the release of the control amino acids have over RNA synthesis in Saccharomyces carlsbergensis N.C.T.C. 74. 2. The antibiotic causes a gradual deceleration of RNA formation. After incubation for 60min. at 30 degrees RNA synthesis usually proceeds at a rate only a few per cent of that of the untreated control. 3. In the presence of cycloheximide two types of RNA accumulate in the cell: soluble RNA and a high-molecular-weight RNA. The latter has a base composition intermediate between those of yeast DNA and yeast ribosomal RNA, and sediments in a sucrose gradient at a rate faster than that of the 23s ribosomal RNA component. 4. Yeast ribosomal RNA contains methylated bases. Judged from the incorporation of [Me-(14)C]methionine, the extent of methylation of ribosomal RNA is about 20% of that of the ;soluble' RNA fraction. The high-molecular-weight RNA formed in the presence of cycloheximide is less methylated than normal RNA. In this case the sucrose-density-gradient sedimentation patterns of newly methylated and newly synthesized RNA do not coincide. 5. In the presence of cycloheximide, polysomal material accumulates, indicating that messenger RNA is formed. 6. The effect of the antibiotic on protein and RNA synthesis can be abolished by washing of the cells. The RNA that has accumulated during incubation of the cells with the antibiotic is not stable on removal of cycloheximide. 7. The results presented in this study are discussed in relation to the regulation of RNA formation in yeast.

Alkylation↗
PubMed1977

Regulation of mammalian protein synthesis in vivo. Stimulated liver ribonucleic acid synthesis in vivo after cycloheximide treatment.

1. As shown by a double-radioisotope technique in vivo, at a non-lethal dose of cycloheximide, a stimulation of nuclear RNA synthesis occurred by 12 h after the treatment; the stimulation lasted over 48 h. Analysis of radioactive nuclear RNA by gel electrophoresis demonstrated that most of the cycloheximide-stimulated synthesis could be accounted for by known rRNA precursors (45 S, 41 S, 32 S and 28 S). 2. During the inhibitory phase of protein synthesis, 2 h after cycloheximide treatment, synthesis of the poly(A)-containing mRNA isolated from the cytoplasmic ribonucleoprotein complexes with an oligo(dT)-cellulose column was stimulated, whereas the synthesis of rRNA was slightly inhibited. However, during the stimulatory phase of protein synthesis, 24 h after cycloheximide treatment, the syntheses of both poly(A)-containing mRNA and rRNA were enhanced. 3. Kinetic studies revealed that the newly synthesized RNA species were transported from the nuclei, integrated into the ribonucleoprotein complexes, and associated with both free and membrane-bound polyribosomes. 4. These data corroborate our proposal that the stimulated protein synthesis after cycloheximide administration involves gene transcription.

Animals↗
PubMed1980

The effect of cycloheximide on the glycosylation of lactating-rabbit mammary glycoproteins.

1. Cycloheximide inhibited immediately the incorporation of L-[4,5-3H]leucine and D-]2-3H]mannose into mammary proteins, suggesting that the mannosylation of mammary glycoproteins requires the continued supply of newly synthesized polypeptides. 2. The incorporation of radioactivity from N-acetyl-D-[1-14C] glucosamine into protein was not inhibited until approx. 30 min after cycloheximide addition. Much (greater than 90%) of this radioactivity was present as N-acetylgalactosamine. 3. N-Glycosylation appears to be inhibited immediately by cycloheximide due to a lack of newly synthesized acceptor polypeptides, whereas O-glycosylation continues for 30 min, the time taken for acceptor peptides to move from their site of synthesis to the Golgi region and for completion of glycosylation. 4. There was a transient increase in the incorporation of mannose into lipid-linked oligosaccharide in the presence of cycloheximide, followed by a decrease in the radioactivity in this fraction. 5. The major lipid-linked oligosaccharide extracted from explants incubated for 2h in the presence of cycloheximide (6-7 monosaccharide units) was smaller than that extracted from control explants (10-12 monosaccharide units).

Animals↗