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PubMed1983

The protein synthesis inhibitors from wheat, barley, and rye have identical antigenic determinants.

We have purified the protein synthesis inhibitors from wheat (tritin) and investigated their antigenic relationship to inhibitors from other grains and more distantly related plants. Three forms of tritin (tritin 1, 2, and 3) indistinguishable with regards to their molecular weight and enzymatic properties were found. Antiserum against the most abundant tritin, tritin 2, cross reacted with tritin 1, tritin 3, and with the translation inhibitors from barley and rye, but not with other plant-derived translational inhibitors. The results indicate that only closely related plants contain antigenically similar protein synthesis inhibitors.

Epitopes↗

PubMed1995

Transitory effects of intracerebral administration of protein synthesis inhibitors on rat's spontaneous behavior.

In order to evaluate whether the effects of the local administration of protein synthesis inhibitors are transient or permanent, small volumes of cycloheximide, 2-deoxy-d-galactose, tetrodotoxin, and saline solution were stereotaxically administered in the amygdala, substantia nigra, and nucleus basalis magnocellularis of naive male adult Wistar rats. Three spontaneous activities (feeding, drinking, locomotion) were continuously recorded. 12 groups of animals were housed in activity cages for 6 consecutive days with a light/dark schedule (LD 12:12). The active compounds at doses sufficient to cause only limited effects were administered at the beginning of the light period of the fourth day. During the initial three days spontaneous activities remained constant, following the normal circadian distribution of rodents. Cycloheximide and tetrodotoxin administrations were followed by transient site-specific and activity-specific changes, which occurred only during the fourth and fifth day. The results show that protein synthesis inhibitors can be locally administered into the CNS at doses affecting only limited subcortical structures. The observed modifications of the three spontaneous activities were all transient and were always followed by complete recovery within 48 hours, thus confirming previous biochemical data. Therefore, the local injection of protein synthesis inhibitors, like tetrodotoxin, lidocaine or other compounds, can be employed to induce transient functional effects on well delimited brain structures in order to study the time-course of the mechanism of mnemonic trace formation.

Amygdala↗

PubMed2001

Induction of cell death in arabidopsis by superoxide in combination with salicylic acid or with protein synthesis inhibitors.

Induction of programmed cell death (PCD) by oxidative stress is a widespread phenomenon in all living organisms. The degree of cell death depends on the concentration of oxidants and on environmental and physiological conditions. In plants, generation of reactive oxygen intermediates (ROI) occurs during many biotic and abiotic stresses. Recently, a number of spontaneous cell death mutants have been isolated in Arabidopsis. In one of the mutants (lsd1) induction of PCD has been attributed to superoxide (O(2)(*)(-)). Here we show that while in wild type plants generation of superoxide is symptomless, combination of O(2)(*)(-) with salicylic acid or with inhibitors of protein synthesis induced PCD. Cell death induced by these treatments was suppressed by protease inhibitors, indicating an active response. PCD induced by both treatments was preceded by nuclear condensation, which is a hallmark of apoptosis in plants and animals. These results may explain increased sensitivity to oxidative stress under certain physiological conditions, associated with high levels of salicylic acid or decrease in protein synthesis.

Apoptosis↗

PubMed1992

Protein synthesis inhibitors, like growth factors, may render resting 3T3 cells competent for DNA synthesis: a radioautographic and cell fusion study.

Serum-deprived (0.1-0.2%) resting NIH 3T3 mouse fibroblasts pre-incubated with cycloheximide (7.5 micrograms/ml), or puromycin (10 micrograms/ml), were fused with stimulated cells taken 10 h after changing the medium to one containing 10% serum, and DNA synthesis was investigated in the nuclei of monokaryons, homodikaryons and heterodikaryons using radioautography with the double-labelling technique. Pre-incubation of resting cells with inhibitors of protein synthesis for 1-4 h abolished their ability to suppress DNA synthesis in stimulated nuclei in heterokaryons. Three hours after the removal of cycloheximide from the medium, the resting cells acquired once again the inhibitory capacity for entry of stimulated nuclei into the S period. This inhibitory influence disappeared also in the case of post-fusion cycloheximide application as well as following an 8-12 h pre-treatment of resting cells with actinomycin D (1 microgram/ml) prior to fusion. Pre-incubation of resting cells for 12 h with PDGF (1 u/ml-1) followed by an 8-48 h incubation in serum-free medium stimulated the onset of DNA synthesis. A brief exposure (45 min) of resting cells to cycloheximide (7.5 micrograms/ml), or puromycin (7.5 micrograms/ml), exerted a similar effect, inducing by itself the entry of cells into the S period. The results support the assumption that acquirement, by resting cells, of competence for DNA replication includes as a necessary step the down-regulation of intracellular growth inhibitors whose formation depends on protein synthesis.

3T3 Cells↗

PubMedDate not supplied

[Effect of protein synthesis inhibitors on the growth and biosynthetic activity of Trichothecium roseum].

The effect of inhibitors of protein synthesis on growth was studied with Trichothecium roseum producing thichothecin and fibrinolytic enzymes. Levomycetin, acridine orange and polymyxin inhibited the biomass accumulation, the growth rate, and the biosynthesis of fibrinolytic enzymes, particularly at the early stages of fungal growth. This effect was found either when the substances were added at the same time as the mycelium was inoculated, or when they were introduced 24 hours after the beginning of cultivation. The substances inhibited the differentiation of the substrate mycelium of T. roseum. Substrate conidia, budding and initial cells were formed by the mycelium only after 72--96 hours of growth.

Acridine Orange↗

PubMed1991

Abundance of hepatic metallothionein mRNA is increased by protein-synthesis inhibitors. Evidence for transcriptional activation and post-transcriptional regulation.

Ongoing protein synthesis is a prerequisite in the expression of some genes. We studied the effect of various protein synthesis inhibitors on the expression of the avian metallothionein (MT) gene. Chicken embryonic hepatocytes in culture were exposed to various concentrations of cycloheximide, puromycin and pactamycin. At concentrations which decreased total protein synthesis by about 90% each inhibitor increased MT mRNA accumulation approx. 5-fold at 9 h of incubation. Incubation with puromycin or zinc for 2 h markedly increased the rate of MT gene transcription. Estimates of the half-life of MT mRNA by using actinomycin D suggested for cycloheximide, but not puromycin, decreased the decay rate of MT mRNA. These data suggest the potential for post-transcriptional regulation of the avian MT gene. We conclude that different antibiotics increase the accumulation of hepatocyte MT mRNA by different mechanisms and that the possibility of multiple mechanisms should be considered in other studies of the role of protein synthesis in gene expression.

Animals↗

PubMed1983

Chinese hamster cells can be reversibly blocked before mitosis with the protein synthesis inhibitor, emetine.

The inhibition of protein synthesis in eukaryotic cells will prevent them from entering mitosis. Emetine inhibits peptide elongation. When it was added to asynchronous populations of Chinese hamster ovary (CHO) cells, the mitotic index decreased sharply 30 to 40 min later. It was found that the inhibitory effect of emetine could be reversed when it was removed and the reversibility was dependent on both the initial concentration of emetine and the pH of the medium. Cell populations that were blocked by emetine for up to 2h showed a four- to fivefold increase in mitotic index approximately 1 h after the emetine was removed. These results indicate that there is a point or period in G2 phase at which critical 'mitotic proteins' are being synthesized, and if their synthesis is interrupted cells will fail to enter mitosis.

Animals↗

PubMed1994

The effect of protein synthesis inhibitors on the glycosylation site occupancy of recombinant human prolactin.

The relationship between synthesis and N-linked glycosylation site occupancy of recombinant human prolactin produced from C127 cells was studied with the aid of a battery of protein synthesis inhibitors. Non-lethal concentrations of sodium fluoride, gougerotin, puromycin, anisomycin, and emetine did not alter site occupancy, but low concentrations (< 10 micrograms ml-1) of cycloheximide increased the fraction of secreted prolactin bearing oligosaccharide from 20% to 80% of the total. Cycloheximide is an inhibitor of the elongation step of protein synthesis. The observed increase in glycosylation site occupancy upon addition of cycloheximide is consistent with the current opinion that the initial glycosylation event occurs cotranslationally during a limited time period. Cycloheximide may extend this time period by reducing elongation rate. However, the absence of any effect from treatment with other inhibitors of elongation suggests that cycloheximide is unique in its behavior on this system.

Amidohydrolases↗

PubMed1995

Transcriptional regulation of PS-IAA4/5 and PS-IAA6 early gene expression by indoleacetic acid and protein synthesis inhibitors in pea (Pisum sativum).

The transcription of two genes, PS-IAA4/5 and PS-IAA6, in pea is induced by indoleacetic acid (IAA) and protein synthesis inhibitors such as cycloheximide (CHX) and anisomycin (ANI). Induction by IAA is rapid, taking 5 and 7.5 minutes for PS-IAA4/5 and PS-IAA6, respectively, and is independent of IAA concentration and whether IAA has a free or esterified carboxyl group (ethyl-IAA). The rate of mRNA accumulation, however, is dependent on hormone concentration, and is greater with IAA than with ethyl-IAA. The turnover rates (t1/2) of the PS-IAA4/5 and PS-IAA6 mRNAs are 60 and 75 minutes, respectively, and are not affected by IAA. CHX or ANI induce the transcription of PS-IAA4/5 and PS-IAA6 more slowly than IAA (5 to 10 minutes for PS-IAA4/5 and 20 minutes for PS-IAA6). While protein synthesis inhibitors stabilize both mRNAs, the rapidity of induction by CHX and ANI cannot be accounted for solely by mRNA stabilization. The relationship between mRNA induction and protein synthesis inhibition does not obey Michaelis-Menten kinetics, but rather is best described by a hyperbolic curve, suggesting the release of transcriptional repression by the inhibition of protein synthesis. RNA expression experiments with transgenic tobacco seedlings or with transfected pea protoplasts using PS-IAA4/5 promoter GUS or CAT fusions reveal that CHX transcriptionally activates PS-IAA4/5 gene expression. Thus, protein synthesis inhibitors have a dual effect on PS-IAA4/5 and PS-IAA6. (1) They stabilize both mRNAs (possibly by a translational arrest-linked process or by preventing the synthesis of a labile nuclease(s)). (2) They activate transcription (possibly by preventing the synthesis or function of a repressor).

Anisomycin↗

PubMedDate not supplied

[Effect of protein synthesis inhibitors on the activity of mitochondrial enzymes of Saccharomyces cerevisiae during desiccation].

The work deals with the effect of carbon sources, presence of protein synthesis inhibitors (cycloheximide and chloramphenicol) and dehydration regime on the enzyme activity of the dried yeast Saccharomyces cerevisiae. The yeast grown on molasses and dried by aeration demonstrated a notable increase of the NADH-dehydrogenase and succinate dehydrogenase activities as compared with the analogously treated yeast grown on ethanol. The latter showed a notable rise only in the activity of NADH-dehydrogenase during slow drying. Addition of protein synthesis inhibitors into the cultivation medium caused no decrease of activities of the above mentioned enzymes of the dried yeasts in any variant under study.

Desiccation↗

PubMed1988

Effect of mitochondrial protein synthesis inhibitors on erythroid differentiation of mouse erythroleukemia (Friend) cells.

When mouse erythroleukemia (MEL) cells were incubated in the presence of chloramphenicol (a specific inhibitor for mitochondrial protein synthesis) during the early stage of in vitro erythroid differentiation, the number of induced erythroid cells was greatly reduced. By use of cell fusion between two genetically marked MEL cells, this finding was further investigated. We found that the drug, along with other agents which inhibit mitochondrial protein synthesis, blocked the induction and turnover of the DMSO-inducible intracellular-erythroid-inducing activity (differentiation-inducing factor II) in a manner similar to that of cycloheximide, an inhibitor for nuclear protein synthesis. The inhibitory effect was confirmed by directly assaying differentiation-inducing factor II in the cell extracts. These results strongly suggest that mitochondrial protein synthesis is closely associated with in vitro erythroid differentiation of MEL cells.

Animals↗

PubMed1969

Infection structures from rust urediospores: effect of RNA and protein synthesis inhibitors.

Urediospores of Puccinia graminis tritici, floated on buffer, produce infection structures when subjected briefly to 30 degrees C soon after germination. Inhibitors of RNA synthesis interfere with the difierentiation of infection structures if present during this heat treatment. Inhibitors of protein synthesis prevent differentiation if present following heat treatment. Apparently infection structure formation is accompanied by synthesis of RNA, and the completion of infection structure development requires protein synthesis.

Basidiomycota↗

PubMed1985

Influence of protein synthesis inhibitors on regulation of extent of O-acetylation of gonococcal peptidoglycan.

The effects of protein synthesis inhibitors on the extent of O-acetylation of Neisseria gonorrhoeae peptidoglycan (PG) and on the resistance of PG to degradation by human PG hydrolases were examined. Addition of chloramphenicol, tetracycline, and streptomycin (in amounts equal to approximately twice their respective MICs) rapidly increased the level of O-acetylation of [3H]glucosamine-labeled N. gonorrhoeae FA19 PG from 46% to about 70% and simultaneously enhanced the resistance of the PG to degradation by human polymorphonuclear leukocyte lysozyme. Entry into the stationary phase also enhanced O-acetylation of FA19 PG, but neither protein synthesis inhibitors nor the stationary phase had a detectable effect on the O-acetyl-deficient, lysozyme-sensitive PG of N. gonorrhoeae RD5. Mild alkali treatment of PG derived from chloramphenicol-treated FA19 specifically removed O-acetyl groups and simultaneously reduced the extents of O-acetylation and polymorphonuclear leukocyte lysozyme resistance to the level of RD5 PG, suggesting that the O-acetyl substituents were solely responsible for the increased PG hydrolase resistance of PG from chloramphenicol-treated FA19. Pulse-chase experiments indicated that the drug-mediated enhancement of O-acetylation was limited to newly assembled PG. In summary, conditions favoring unbalanced macromolecular synthesis and bacteriostasis increased the level of O-acetylation and the PG hydrolase resistance of gonococcal PG. Similar conditions encountered by gonococci in vivo might potentiate the pathobiological consequences of PG-host interactions.

Acetylation↗

PubMed1992

Protein synthesis inhibitors differentially superinduce c-fos and c-jun by three distinct mechanisms: lack of evidence for labile repressors.

Protein synthesis inhibitors strongly augment and prolong the usually transient induction of c-fos and c-jun by growth factors, phorbol esters etc., a phenomenon termed superinduction which is conventionally regarded as a secondary consequence of translational arrest. Our recent demonstration that some inhibitors can act positively as nuclear signalling agonists compromises this view and necessitates a re-evaluation of superinduction. First, we show that labile repressors, widely postulated to act negatively on diverse superinducible genes, are not involved in regulating c-fos and c-jun. Secondly, two components of c-fos and c-jun superinduction, namely the delay in shutting off transcription and stabilization of their mRNAs, arise from translational arrest and are common to all protein synthesis inhibitors. Thirdly, the recently described capacity to act positively as nuclear signalling agonists to stimulate pp33/pp15 phosphorylation is restricted to compounds such as anisomycin and cycloheximide; these, but not emetine or puromycin, will induce c-fos/c-jun on their own. Fourthly, the translational arrest-related components of superinduction are dissociable from the signalling agonist effects at sub-inhibitory concentrations of anisomycin, under which conditions a new type of c-fos/c-jun superinduction with 'spike' kinetics is observed. Finally, we show that in response to EGF plus anisomycin, the nuclear signalling responses are themselves augmented and prolonged in a manner that corresponds to c-fos/c-jun superinduction under these conditions.

Animals↗

PubMedDate not supplied

[Effect of protein synthesis inhibitors on the vicasol-induced change in the content of the thermostable antifactor Xa in the blood serum].

Content of a thermostable inhibitor of thrombinogenesis (antifactor Xa) was decreased in blood serum after administration of pellentan. Subsequent treatment with vicasol normalized at the accelerated rate the antifactor Xa content in blood serum. Administration of the inhibitors of protein synthesis (vincrystine, actinomycin D, toyomycin, tetracycline--inhibitors of RNA polymerase, elongation, posttranscriptional conversions of mRNA and of translation processes, respectively (did not alter distinctly the vicasol effect--decrease in antifactor Xa content of blood serum. Vitamin K appears to participate in formation of the active molecule of the inhibitor of thrombinogenesis at the postribosomal step as shown in study of several other blood plasma procoagulants.

Animals↗

PubMedDate not supplied

[Effect of the protein synthesis inhibitor chloramphenicol on the basic growth indices of continuous and periodic Bacillus megaterium cultures].

The action of chloramphenicol, a specific inhibitor of bacterial growth and an inhibitor of protein synthesis, was studied in the conditions of continuous and batch cultivation. Steady states of the population within the range of D from 0.2 to 0.7 hr-1 were obtained at a concentration of the antibiotic equal to 20 microgram per liter. The shape of the chemostat curve in the presence of chloramphenicol in the medium indicates that the antibiotic slightly decreases mu max and considerably diminished Y. A change of limiting factors occurs along the chemostat curve at different dilution rates (0.2, 0.4 and 0.7 hr-1): one-, two- and three-factor effects on the population were observed. Steady states of the population in the chemostat are possible by chloramphenicol concentrations of 10 to 100 microgram per litre; in this case, cellular metabolism changes in the following nonspecific way: less effective energy processes are activated, the Y decreases as well as protein content in the cells, but the content of poly-beta-hydroxybutyric acid in the biomass increases. If chloramphenicol is taken at a concentration of 1000 microgram per litre (a dose strongly inhibiting the growth rate), other changes specific for this inhibitor are found: the content of protein decreases while that of RNA increases, and substances of nucleotide nature are released into the medium. The changes remain for many generations. The data show that it is possible to change the ratio between cell polymers in growing population.

Bacillus megaterium↗

PubMed2002

Toxicity of cylindrospermopsin to the brine shrimp Artemia salina: comparisons with protein synthesis inhibitors and microcystins.

The Artemia salina bioassay was successfully applied to the analysis of the hepatotoxic cyanobacterial alkaloid and protein synthesis inhibitor, cylindrospermopsin. A dose-dependent response in mortality was observed for purified cylindrospermopsin and LC(50) values decreased with time from 8.1 to 0.71 microg/ml(-1), between 24 and 72 h, respectively. Cylindrospermopsin was slightly less potent than micro cystin-LR, with similar LC(50) values on a gravimetric basis, but was more toxic to A.salina than the protein synthesis inhibitors, cycloheximide, chloramphenicol and tetracycline. Cylindrospermopsin-containing strains of the cyanobacterium Cylindrospermopsis raciborskii were found to be toxic to A.salina and the LC(50) concentration for these strains over time was greater than the LC(50) for purified cylindrospermopsin, with the exception of C. raciborskii strain CR1.

Alkaloids↗

PubMed1990

Induction and superinduction of auxin-responsive mRNAs with auxin and protein synthesis inhibitors.

We have identified a class of small mRNAs (approximately 0.5 kilobases), referred to as small auxin-up RNAs (SAURs), that increases in abundance within minutes after auxin application to excised elongating hypocotyl sections of soybean. In this study, we present evidence that SAURs accumulate in the absence of auxin when protein synthesis is inhibited. Superinduction of SAURs occurs if the synthetic auxin 2,4-dichlorophenoxyacetic acid is added under conditions where protein synthesis is inhibited. Transcription run-on experiments with isolated nuclei show that, unlike 2,4-dichlorophenoxyacetic acid, protein synthesis inhibitors do not activate transcription of the SAUR genes. These results suggest that protein synthesis inhibitors act by stabilizing SAURs and that some labile protein(s) are involved in the rapid turnover of SAURs. This stabilization is not observed with GH3, another auxin-inducible mRNA. Whether induced with 2,4-dichlorophenoxyacetic acid or cycloheximide, SAURs are primarily expressed in epidermal and cortical cells of elongating hypocotyl sections, with little or no expression in vascular tissue. Unlike 2,4-dichlorophenoxyacetic acid-induced SAUR accumulation, the increase in abundance of SAURs induced by cycloheximide is transient, with a peak approximately 1 h after inhibitor addition. Complete inhibition of protein synthesis is not required for SAUR accumulation in the presence of protein synthesis inhibitors.

2,4-Dichlorophenoxyacetic Acid↗