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 505 records · Page 28Linked to original sources
PubMed1988

Regression of autophagic vacuoles in pancreatic acinar, seminal vesicle epithelial, and liver parenchymal cells: a comparative morphometric study of the effect of vinblastine and leupeptin followed by cycloheximide treatment.

Treatment of mice with both leupeptin (0.06 mg/g body wt) and vinblastine (0.05 mg/g body wt) for 2 h caused a many-fold enlargement of the autophagic-lysosomal compartment of pancreatic acinar, seminal vesicle epithelial, and liver parenchymal cells. In all three types of cells a predominance of large, dense bodies was seen after leupeptin treatment and that of typical autophagic vacuoles were seen after vinblastine treatment. An exponential decrease of the volume fraction of autophagic vacuoles was observed in leupeptin-treated cells after the administration of cycloheximide (0.2 mg/g body wt). The half-life of autophagic vacuoles estimated from the decay curve was 5.3, 5.7, and 6.6 min for pancreatic, seminal vesicle, and liver cells, respectively. Our data suggest that sequestered cytoplasmic material rapidly enters the lysosomes in leupeptin-treated cells and accumulates in this compartment. In contrast, no regression of the autophagic vacuole compartment of pancreatic and seminal vesicle cells was observed after the administration of cycloheximide to animals pretreated with vinblastine, and only a slight decrease was seen in liver cells. These observations show that the lifetime of autophagic vacuoles is prolonged by vinblastine resulting in their accumulation in the cells. However, our measurements also lend support to the view that in addition to the accumulatory effect on undegraded cytoplasmic material, stimulation of sequestration may play a role in the enlargement of the autophagic lysosomal compartment after treatment with leupeptin as well as with vinblastine in all three types of cells investigated.

Animals↗
PubMed1994

Enhancement of inducible-type NO synthase gene transcription by protein synthesis inhibitors. Activation of an intracellular signal transduction pathway by low concentrations of cycloheximide.

Treatment of mouse macrophage-like RAW 264.7 cells with certain protein synthesis inhibitors is followed by accumulation of the mRNA for the inducible isoform of nitric oxide synthase (i-NOS). The activity of these compounds on the i-NOS gene in RAW 264.7 cells was analyzed here in detail. Results show that both cycloheximide and anisomycin can efficiently induce i-NOS mRNA, even when used at concentrations so low (0.25 microgram/ml) to have only negligible effects on protein synthesis; puromycin, on the other hand, shows only a limited effect on i-NOS mRNA expression, detectable only when cells are treated with higher concentrations of inhibitor (25 micrograms/ml). In RAW 264.7 cells, low concentrations of cycloheximide trigger an immediate-early gene response, as indicated by induction of c-fos and JE mRNAs, and can efficiently activate transcription of transiently transfected recombinant reporter genes including either the i-NOS or the c-fos gene promoters.

Amino Acid Oxidoreductases↗
PubMed1986

The in vitro effects of cyclic nucleotides, cyanoketone, and cycloheximide on the production of estradiol-17 beta by vitellogenic ovarian follicles of goldfish (Carassius auratus).

The effects of human chorionic gonadotropin (HCG), forskolin, cyclic nucleotides, the phosphodiesterase inhibitors IBMX and theophylline, cyanoketone, and cycloheximide on the production of estradiol-17 beta by isolated ovarian follicles of vitellogenic goldfish (Carassius auratus) were examined using 18-hr incubations. HCG and all test agents which are known to increase intracellular concentrations of cAMP significantly stimulated the production of estradiol-17 beta. However, dibutyryl cGMP was unable to stimulate estradiol-17 beta production at any concentration used (1-10 mM). Cyanoketone at a concentration of 1 micrograms/ml completely blocked forskolin-induced estradiol-17 beta production. Even in the presence of cyanoketone, however, forskolin stimulated conversion of exogenous testosterone to estradiol-17 beta in a dose-dependent manner, suggesting the involvement of an adenylate-cyclase system in the induction of aromatase activation by vitellogenic follicles of goldfish. Cycloheximide also completely abolished HCG-induced estradiol-17 beta production when this inhibitor was added within the first 1 hr after the addition of HCG. These results provide evidence that the stimulation of estradiol-17 beta by goldfish vitellogenic follicles in response to HCG is dependent upon the synthesis of new protein.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Thyroid hormone receptor induction by triiodothyronine in tadpole erythrocytes in vivo and in vitro and the effect of cycloheximide and actinomycin-D.

Tadpole erythrocyte nuclei contain specific T3 binding sites which increase in number during spontaneous or T3-induced metamorphosis. In the present studies the increase in the number of T3 binding sites after a T3 injections appeared to be completely prevented by cycloheximide and actinomycin D, inhibitors of protein synthesis and RNA synthesis, respectively. However, in some experiments the effect was not statistically significant. The increase in sites was prevented only if the inhibitors were administered at 0 or 24 hr after T3 injection, but not at 48 or 72 hr after T3. When tadpole erythrocytes were incubated with T3 in vitro in M199 culture medium, the number of nuclear T3 binding sites increased within 48 hr. This increase was highly sensitive to inhibition by cycloheximide (maximal at 1 x 10(-6) M) or actinomycin D (maximal at 0.02 micrograms/ml). These inhibitor concentrations only slightly reduced the incorporation of labeled precursors. The T3 concentration required to induce a half-maximal increase in binding sites in vitro was about the same as the T3 concentration at which half the binding sites were occupied. The T3 binding sites had a high affinity for thyroid hormone analogs which stimulate metamorphosis. These results support the designation of the T3 binding sites as T3 receptors. They show that the tadpole erythrocytes respond to T3 with an increase in the number of T3 binding sites without the involvement of other tissues. It is proposed that this is a receptor induction involving synthesis of RNA and protein.

Animals↗
PubMed1989

Effect of the administration of cycloheximide to thioacetamide-primed rats or partial-hepatectomized rats on the RNA polymerase I activity in isolated nuclei of liver.

1. Twenty-four hours after administration of thioacetamide to normal rats, the activity and amount of RNA polymerase I in isolated liver nuclei were almost doubled. 2. When cycloheximide was administered to the drug-treated rats and normal rats 1 or 2 hr before death, the reduction in the activity was of the same degree, that is, about half of the activity of liver nuclei from normal rats. 3. Partial hepatectomy also caused about 2-fold increase in the RNA polymerase I activity in isolated liver nuclei after 16 hr, but the increased activity was almost completely abolished by injection of cycloheximide 1-3 hr before killing.

Acetamides↗
PubMed1989

The effects of endotoxin pretreatment on subsequent challenge of mice with cycloheximide and a small dose of endotoxin.

Mice treated with 15.0 micrograms of S. enteritidis endotoxin are completely protected against the coagulopathic effects, but only partially protected against the fatal glucocorticoid deficiency which follow an otherwise lethal challenge with cycloheximide and 5.0 micrograms of the same endotoxin given 3 days later. Hydrocortisone treatment results in survival of all such tolerant, challenged animals. The protection conferred against occlusion of glomerular capillaries by fibrin coagula is abolished by EACA, suggesting that tolerance has induced high levels of fibrinolytic activity by the time of challenge, and evidence indicates that this protective degree of fibrinolytic activity persists for more than 24 h after cycloheximide and endotoxin challenge.

Aminocaproic Acid↗
PubMed1989

Cycloheximide-resistant gene of Epstein-Barr virus in freshly infected B lymphocytes.

The transcription of latent Epstein-Barr viral (EBV) genes, i.e., genes encoding EBNA-1, EBNA-2, EBNA-3A, -3B, -3C, and LMP, were detected in human tonsillar lymphocytes early after infection with EBV. Transcription of the BHLF-1 open reading frame was also detected at this initial phase of immortalization. Cycloheximide treatment inhibited the transcription of all the latent EBV genes but not BHLF-1. These results suggest that BHLF-1 might be considered an immediate-early gene of EBV. Cycloheximide treatment of EBV-infected cells reduced not only the degree of the transcription but also the size of the transcript for EBNA-2. We hypothesize that the immediate-early expression of BHLF-1 may be required for the enhanced transcription of the viral genes in lymphocytes early after infection with EBV.

Antigens, Viral↗
PubMed1983

Activation of xanthine dehydrogenase during the prenatal period through L-thyroxine, thiourea and cycloheximide.

Xanthine dehydrogenase activity in the liver of embryonic chicks has been shown to be inducible by L-thyroxine, thiourea, and cycloheximide. Results reported here indicate different mechanisms underlying the activation through L-thyroxine on the one hand, and through thiourea and cycloheximide on the other. Using hepatocyte suspension and homogenized liver, it has been shown that prenatal activation of xanthine dehydrogenase results in increased rate of uric acid formation from nucleic acids and purine derivatives, but not from amino acids.

Animals↗
PubMed1982

Transcription in aging: the response of rat liver nuclear RNA polymerases to cycloheximide in vivo.

Experiments were performed to address the known relationship between diet and longevity. The acute response of rat liver nuclear RNA polymerases to inhibition of protein synthesis by cycloheximide (10 mg/kg) was quantitated in rats of varying ages. Thirty minutes after cycloheximide administration, there was a "compensatory" 1.5--2-fold increase in RNA polymerase II activity at all ages. Nucleolar RNA polymerase I activity was significantly diminished only up to 4 months, indicating a loss in tight control coupling of protein synthesis to rRNA synthesis with age.

Aging↗
PubMed1976

Modulation of cycloheximide-resistant memory by sympathomimetic agents.

Amphetamine overcomes the amnesia caused by cycloheximide (CXM) provided it is administered closely following the learning trial. In day-old chickens with one trial passive avoidance learning, there is a short-term, labile memory existing for 90 min following training under the influence of CXM. Amphetamine has been shown to keep the memory at precisely the level exhibited by the labile, cycloheximide-resistant memory trace at the time of injection. Norepinephrine, methoxamine (an alpha adrenergic stimulant) and isoprenaline (a beta adrenergic stimulant) each mimic the amphetamine effect in CXM-pretreated chickens. That the action of amphetamine could be due to its release of norepinephrine is supported by the finding that it could be blocked by both alpha adrenergic (piperoxane) and beta adrenergic antagonists (propranolol). It has been suggested that this labile memory trace depends on the functioning of a sodium pump. Norepinephrine may be modulating memory formation by an action on the sodium pump since in preliminary biochemical assays norepinephrine stimulated the sodium pump (Na+/K+ ATPase) activity in chicken forebrain total homogenate.

Amphetamine↗
PubMed1980

Prostaglandin production by minced carrageenin granuloma tissue of rats and its inhibition by dexamethasone and cycloheximide.

Seven-day-old carrageenin granuloma tissue of rats, when incubated in organ culture, produced 6-keto-prostaglandin F1 alpha, prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2 in ratios of 16/7/1/1, respectively. Indomethacin (1 microgram/ml) inhibited this cyclooxygenase-mediated arachidonic acid metabolism. Dexamethasone (1 microgram/ml) also inhibited this metabolic cascade. Its inhibitory effect was not immediate; preincubation of the tissue with dexamethasone potentiated its inhibitory effectiveness. Cycloheximide (0.1 to 10 microgram/ml) also inhibited prostaglandin production. The inhibitory mechanism by cycloheximide of prostaglandin production was discussed in relation to that by dexamethasone.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Developmental changes in the open time and conductance of acetylcholine receptors in aneural cultured Xenopus myocytes treated with cycloheximide or tunicamycin.

Aneural cultures of Xenopus myocytes were treated with cycloheximide or tunicamycin in order to determine the influence of continued protein synthesis and insertion of glycosylated acetylcholine (ACh) receptor proteins on developmental changes in ACh-activated single-channel events. The developmental stage of the cultures was estimated from the stage of intact embryos maintained at the same temperature as the cultures. Single-channel recordings (5 x 10(-7) M ACh) from untreated cultures revealed primarily low conductance (27.4 +/- 0.6 pS) events for the first 14 h in culture (temperature = 23-25 degrees C) and a second high conductance class of events (42.5 +/- 0.9 pS) at later developmental stages (after Stage 28). Treatment with cycloheximide (at Stage 28) or tunicamycin (at Stage 22) produced significantly (P less than 0.01) fewer high conductance events at later stages (Stages 31-47), but had no effect on the conductance or open time of the low conductance event. A significant decrease (Chi square, P less than 0.05) in ACh sensitivity was observed at Stage 27 in myocytes treated with tunicamycin at Stage 22. The results strongly suggest that the low and high conductance events represent two distinct receptor molecules synthesized at different developmental stages. The tunicamycin results also suggest that a developmental reduction in the mean open time of low conductance events in untreated cultures does not depend upon the continued insertion of newly synthesized receptors.

Acetylcholine↗
PubMed1982

Long-term effects on motor activity induced by apomorphine or scopolamine after intracerebral injections of cycloheximide or glutamate shortly after hatching in chickens.

Compared to controls, bilateral forebrain injections of cycloheximide or glutamate in 2-day-old chicks resulted in significantly less activity in response to intraperitoneal injections of the dopaminergic agonist, apomorphine, or the cholinergic antagonist, scopolamine, when tested on stabilimeters four weeks later. These preliminary results are consistent with the idea that amongst other effects neonatal injections of cycloheximide or glutamate may alter dopaminergic and cholinergic neurotransmitter mechanisms involved in motor behavior in birds.

Animals↗
PubMed1982

Operant, open-field and tonic immobility behaviours in chickens with forebrain injections of cycloheximide or glutamate.

Chickens that had received bilateral injections of cycloheximide or glutamate into the forebrain on day 2 of life and tested 4 weeks later showed no deficit in acquisition, performance or extinction of continuously reinforced appetitive key-pecking as compared to control birds injected with saline. However, chickens that had received injections of cycloheximide and were subsequently tested in an open-field apparatus took longer to leave the first square, defaecated more, and pecked, preened and moved about less than controls. They also showed longer durations of tonic immobility. Those injected with glutamate inhibited similar behaviour but were not significantly different from controls in the open field latency to leave the first square, defaecation, or tonic immobility tests. The above treatments have previously been described as producing permanent slowed learning in chickens on a pebble-floor task. Our results suggest that learning mechanisms may not be disrupted as shown by normal performance in a simple operant task but that enhanced emotionality or fear of novelty as revealed in the open field tests may interfere with the expression of learning behaviour in some situations.

Animals↗
PubMed1992

Effects of cycloheximide, brefeldin A, suramin, heparin and primaquine on proteoglycan and glycosaminoglycan biosynthesis in human embryonic skin fibroblasts.

(1) We have isolated radiolabelled proteoglycans and glycosaminoglycans produced by human embryonic skin fibroblasts in the presence of (a) cycloheximide to inhibit protein synthesis or (b) brefeldin A to impede transport between the endoplasmic reticulum and the Golgi complex or (c) suramin, heparin or primaquine to interfere with internalization, recycling and degradation. Effects on glycosaminoglycan synthesis were assayed separately by using exogenous p-nitrophenyl beta-D-xylopyranoside (and [3H]galactose) or 125I-labelled p-hydroxyphenyl beta-D-xylopyranoside as initiators. (2) Inhibition of protein synthesis or blocking of transport to the Golgi complex prevented production of most of the proteoglycans with one exception: Cell-associated heparan sulphate-proteoglycan was still produced at 20% of the control level. (3) Treatment with suramin or heparin resulted in decreased deposition of proteoglycan in the pericellular matrix but increased accumulation of cell-associated proteoglycan. Primaquine blocked all proteoglycan synthesis. (4) In the presence of cycloheximide, exogenous beta-D-xyloside initiated galactosaminoglycan production. In contrast, in brefeldin A-treated cells, synthesis was completely abolished. Not even formation of the linkage-region trisaccharide could be detected. (5) These results suggest that exogenous xyloside enters the endoplasmic reticulum and is subsequently transported to the trans-Golgi complex where all further steps involved in glycosaminoglycan assembly takes place. (6) Heparan sulphate proteoglycan produced by brefeldin A-treated cells could be derived from (a) an intracellular pool of preformed core protein located to the trans-Golgi complex, or (b) resident proteoglycan that was either deglycanated/reglycanated or chain-extended. As combined treatment with suramin and brefeldin A markedly reduced cell-associated proteoglycan production, the latter possibility is favoured.

Anti-Bacterial Agents↗
PubMed1978

Pyrimidine nucleotide synthesis in rat liver after the administration of cycloheximide.

After the administration of cycloheximide (2 mg/kg) the utilization of [2(-14C)]orotic acid for the synthesis of pyrimidine nucleotides of acid-soluble extracts of the liver is not affected for about 7 h. The specific activities of uridine and cytidine components are increased later on, and this increase is higher in the case of cytidine components. Analogous changes undergoes the specific activity of RNA pyrimidine nucleotides. The increased utilization of labeled orotic acid for the synthesis of cytidine nucleotides can be observed also in the kidney and in the small intestine. The enhanced degree of labeling of cytidine nucleotides in vivo cannot be correlated with the activity of cytidine triphosphate synthetase (EC 6.3.4.2) of liver cytosol estimated in vitro. The amination of UTP is suppressed at later intervals after the application of cycloheximide. The same holds true for the activity of uridine phosphorylase (EC 2.4.2.3),5'-nucleotidase (EC 3.1.3.5) ATPase (EC 3.6.1.3) and of liver cytosol. The activity of uridine kinase (EC 2.7.1.48) is increased when tested both with uridine and cytidine as substrates. Cytidine deaminase activity (EC 3.5.4.5) raises markedly 3--5 h after the administration of drug; later on it decreases again.

Animals↗
PubMed1976

Different effects of cycloheximide and chloramphenicol on corticosterone production by isolated rat adrenal cells.

Cycloheximide and chloramphenicol both inhibit the stimulating effect of adenocorticotropic hormone (ACTH) on adrenal steroid production. To test whether these inhibitors had andy effect on adrenal steroid production, independent fromthe mechanism of action of ACTH we investigated their effect on the conversion of 25-hydroxycholesterol into corticosterone in isolated rat adrenal cells. Cycloheximide, both in the absence and in the presence of ACTH, had no effect on this conversion. Chloramphenicol inhibited the conversion of 25-hydroxycholesterol into corticosterone whether ACTH has no direct efeect on the cholesterol side-chain cleaving system. The inhibition by chloramphenicol of the ACTH-stimulated steroid production is at least partly due to inhibition of one or more of the processes involved in the conversion of 25-hydroxycholesterol into corticosterone.

Adrenal Glands↗
PubMed1983

Effects of isoproterenol and cycloheximide on parathyroid secretion.

Tissue slices or dispersed cells of bovine parathyroid gland were incubated with [3H]leucine to label the intracellular proteins and then tested for their secretory response to isoproterenol and cycloheximide at different calcium concentrations. Secretion of the newly synthesized as well as the older PTH and SP-I was stimulated by isoproterenol at all calcium levels tested, even when it was maximally enhanced by low calcium. Cycloheximide interfered with neither the secretory process nor the secretory response to different stimuli, but decreased the amount of PTH and SP-I secreted. We conclude that the inhibitor decreased the secretion by reducing the supply of PTH and SP-I. Calculations derived from the data reveal that, under most secretory conditions, newly synthesized PTH contributed a major portion of the total hormone secretion in bovine parathyroid cells.

Animals↗