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 181 records · Page 10Linked to original sources
PubMed1984

Rapid qualitative changes in mRNA populations in cultured human lymphocytes: comparison of the effects of cycloheximide and concanavalin A.

To examine the hypothesis that the stimulation of cultured lymphocytes by lectins involves the inactivation of a protein repressor of putative "activation genes," the effects of a protein synthesis inhibitor (cycloheximide) and a lectin (concanavalin A) were compared. Qualitative changes in mRNA populations were assessed by translating RNA prepared from cycloheximide- or lectin-treated cultures in a rabbit reticulocyte lysate. [35S]Methionine-labelled translation products were analysed by two-dimensional polyacrylamide gel electrophoresis. Cycloheximide increased the radioactive labelling of cultured lymphocytes with the RNA precursor [3H]uridine, as previously reported. This was observed during the first 3 h of culture; thereafter, cycloheximide was inhibitory. The period of increased labelling with [3H]uridine coincided with a period of great increase in mRNA corresponding to an acidic protein of a relative mass of approximately 55 000. This mRNA was not detected in RNA prepared from control cultures, but was one of the most abundant mRNA species detected in RNA prepared from cycloheximide-treated cultures. Increases in certain less abundant mRNA species were also noted. However, the mRNAs were not observed in RNA prepared from lectin-treated cultures. If an increase in these mRNAs is important for lymphocyte activation, then the increase must be to an extent not detected by our current methods.

Concanavalin A↗
PubMed1982

Effect of cycloheximide on corticosteroid-induced changes in colonic function.

Chronic parenteral mineralocorticoid and glucocorticoid treatment increases colonic sodium and water absorption and mucosal Na-K-ATPase activity. Cycloheximide, a protein synthesis inhibitor, was utilized to compare the mechanisms of action of these corticosteroids. Rats were injected with 50 or 100 micrograms/100 g body wet cycloheximide every 12 h, 0.5 or 3 mg/100 g deoxycorticosterone (DOCA) daily, or 3 mg/100 g methylprednisolone (MP) daily, singly or in combination for 2 days. In water absorption, transmural potential difference, and the specific activity of Na-K-ATPase were measured. Cycloheximide alone did not alter colonic water, sodium, or chloride absorption or Na-K-ATPase activity but did increase transmural potential difference. DOCA-induced increases in colonic absorption and Na-K-ATPase were completely prevented by cycloheximide. Cycloheximide completely prevented the increase in Na-K-ATPase in MP-treated rats but only partially reduced the MP-induced increase in sodium and water absorption. These results suggest that this enzyme is not the primary site of glucocorticoid action. It remains to be determined whether an increase in Na-K-ATPase activity is a necessary part of the maximal colonic response to chronic glucocorticoid treatment.

Absorption↗
PubMed1986

Prostaglandin E2 and muscle proteolysis: effect of burn injury and cycloheximide.

Rats were subjected to a single hindlimb scald, and 3 days later soleus muscles from the burned and contralateral unburned hindlimbs were studied in vitro. Burned limb muscle released 354% more prostaglandin E2 (PGE2) and 119% more tyrosine than the contralateral uninjured counterpart. Neither the rate of net proteolysis in the uninjured muscle nor the stimulated net proteolysis in the burned limb muscle could be reduced by 90% inhibition of PGE2 production with aspirin or indomethacin. Inhibition of tissue protein synthesis with 5 X 10(-5) M cycloheximide stimulated tyrosine release by soleus muscles of both hindlimbs, but the increment in the burned limb muscle was 167% greater than in the contralateral uninjured counterpart. Concomitantly, cycloheximide decreased PGE2 releases by injured and uninjured muscles 90 and 73%, respectively. This previously unrecognized action of cycloheximide was investigated in soleus muscles of normal uninjured rats. It was found that 1 X 10(-6) M cycloheximide produces a 70% inhibition of muscle PGE2 release and increasing the concentration of inhibitor up to 500-fold does not further decrease PGE2 production. Cycloheximide acts by reducing the availability of endogenous arachidonic acid for PGE2 synthesis.

Animals↗
PubMed1979

Inhibition of spindle assembly by colchicine and of cell cycle by cycloheximide. Comparison and combination of their cytological action on cleavage mitoses.

In cleavage mitoses colchicine (2 x 10(-3) M) does not interrupt the cycle of chromatin and its action is exerted on all the mitotic phases. Cycloheximide (10(-3) M) prevent normal condensation of the chromosomes and breakdown of the nuclear envelope; it brings on various nuclear abnormalities, particularly irregularities in chromosome condensation. At 10(-4) M, cycloheximide allows some mitoses, often abnormal ones, but anaphase is inhibited. The action of colchicine, more efficient upon the spindle, obscures the action of cycloheximide when both substances are associated. In return, cycloheximide imposes its action upon chromosome condensation, so that the structure of the nuclei treated by both substances is determined by cycloheximide.

Animals↗
PubMed1996

Effect of cycloheximide on nuclear maturation of horse oocytes and its relation to initial cumulus morphology.

The period of protein synthesis necessary for meiotic maturation in horse oocytes initially having compact or expanded cumulus cells was studied. Oocytes incubated in the presence of cycloheximide after 0, 4, 8, 12 or 16 h maturation in vitro (total incubation time 24 h) were matured for 24 h, or were incubated with cycloheximide for 24 h and then matured for 24 h. Incubation with cycloheximide from 0 h was effective in suppressing maturation (no significant increase in maturing oocytes compared with controls fixed directly after removal from the follicle) in both expanded and compact groups and was completely reversible, as there was no difference in the proportion of oocytes reaching metaphase II between controls and treatment groups of either cumulus type. Addition of cycloheximide after 4 h maturation resulted in no significant difference in distribution of oocytes compared with addition at 0 h in either cumulus group. A significant decrease in the proportion of germinal vesicle stage oocytes, and an increase in oocytes in metaphase I occurred in oocytes with expanded cumulus cells in the 8 h treatment and in oocytes with compact cumulus cells in the 12 h treatment, compared with oocytes treated after 0 h. A significant increase in the proportion of oocytes at metaphase II occurred in the 12 h treatment for expanded cumulus-oocyte complexes and in the 16 h treatment for compact cumulus-oocyte complexes. These data show that nuclear maturation of horse oocytes can be reversibly suppressed by incubation with cycloheximide from the onset of culture. Oocytes with different initial cumulus type differed in the time required for protein synthesis essential for maturation: expanded cumulus-oocyte complexes required less time to prepare for germinal vesicle breakdown, maturation to metaphase I, and maturation to metaphase II, than did compact cumulus-oocyte complexes.

Animals↗
PubMed1978

Effects of gonadal steroids and cycloheximide on the release of gonadotrophins by rat pituitary cells in culture.

The effects of oestradiol-17beta, testosterone and progesterone alone and together with cycloheximide on the basal and gonadotrophin releasing hormone (Gn-RH)-induced release of gonadotrophins were studied in cultured dispersed rat pituitary cells. In the control group (no steroid treatment), GnRH significantly stimulated the release of LH and FSH; cycloheximide partially inhibited this response, although it had no effect on the basal secretion of gonadotrophins. A dose of 5 ng oestradiol/ml had no significant effect on the response to GnRH; at a dose of 100 ng/ml the GnRH-induced release of LH was significantly augmented whereas the release of FSH was inhibited. Cycloheximide blocked the augmenting effect of oestradiol. The basal release of LH was slightly but significantly inhibited in response to 10 ng testosterone/ml and increased in response to progesterone (200 ng/ml). Testosterone at both dose levels and progesterone significantly inhibited the GnRH-induced release of LH and FSH and in testosterone and progesterone-treated groups, the response to GnRH was inhibited by cycloheximide, but not beyond the levels observed in the control group. It is concluded that steroids can act directly on the pituitary cells, that oestradiol stimulates the GnRH-induced release of LH and that cycloheximide blocks this stimulatory effect. Testosterone and progesterone, on the other hand, partially inhibit the response to GnRH.

Animals↗
PubMed1987

Effects of cycloheximide during the periovulatory period on ovarian follicular FSH, hCG, and prolactin receptors and on follicular maturation in the hamster.

Hamsters were injected sc at 1400 hr on proestrus with either 4 mg cycloheximide (which blocks ovulation but only transiently affects ovarian protein synthesis) or saline and killed at 2-hr intervals until 0400 hr on estrus. After cycloheximide, the first surge of FSH (at 1600 hr) was half the normal value and the second surge of FSH (beginning at 2200 hr) was eliminated. Control follicles at 1400 hr had approximately the same number of FSH and hCG receptors with about one-third as many PRL receptors. Down regulation of FSH and hCG receptors for control follicles occurred by 2400 hr while PRL receptors dropped abruptly 4 hr earlier. Compared to the 1400-hr control values, the maximal loss of FSH, LH, and PRL receptors was 40, 45, and 85%, respectively. Although cycloheximide tended to slightly delay the loss of FSH receptors at 2000-2200 hr it did not prevent the ultimate fall in FSH and hCG receptors; the loss of PRL receptors was accelerated by 4 hr. Cycloheximide prevented or delayed follicular growth, resumption of meiosis, and cumulus expansion. The altered proestrous profile of steroids after cycloheximide (prolonged follicular estradiol and reduced progesterone) is therefore not associated with drastic alterations in the number of FSH and hCG binding sites. On the other hand, PRL receptors represent fast turnover protein(s).

Animals↗
PubMed1991

Activities of APh, gamma-GT, GlDH and GPT and bile acid concentrations in serum after bile duct obstruction and cycloheximide in the rat.

The aim of this study was to investigate the effect of the protein synthesis inhibitor cycloheximide on the serum activities of gamma-Glutamyltransferase, Glutamate dehydrogenase and Glutamate pyruvate transaminase after bile duct obstruction in rats. The results showed that the increase of these enzyme activities after bile duct obstruction is further augmented by cycloheximide. Determinations of total bile acids in serum and liver showed that also the bile acid concentrations rise to a higher level after bile duct obstruction + cycloheximide than after bile duct obstruction alone. It is concluded that the effect of cycloheximide on the serum enzyme activities in extrahepatic cholestasis is produced via an influence on the metabolism of bile acids. This stresses the central role of bile acids for alterations of enzyme activities in extrahepatic cholestasis. Further, the effect of cycloheximide on bile acids after bile duct obstruction has not been reported before.

Alanine Transaminase↗
PubMed1983

Cycloheximide causes accumulation of insulin receptors at the cell surface of cultured fibroblasts.

Incubation of confluent cultures of mouse fibroblasts with cycloheximide caused a time-dependent increase in the binding of 125I-insulin. The increase was concentration-dependent between 0.05 and 3.5 microM cycloheximide and showed a high correlation (r = 0.97) between the increase in 125I-insulin binding and the inhibition of protein synthesis. In the presence of 3.5 microM cycloheximide, insulin binding increased to 236% of control and incorporation of [3H]valine into proteins fell to 10-20% of control. Scatchard analysis of the binding data indicated that cycloheximide-treated cultures had a total of 6.6 X 10(4) binding sites/cell compared to 3.9 X 10(4) sites/cell in untreated cultures. No significant changes in affinity were observed. Other protein synthesis inhibitors also caused an increase in 125I-insulin binding. With 25 mM ethionine and 2 mM sodium fluoride, binding was 155 and 245% of control and incorporation of [3H]leucine into proteins was decreased to 41 and 47% of control, respectively. These results suggest that the accumulation of insulin receptors at the cell surface following treatment with cycloheximide results from inhibition of synthesis of proteins involved in insulin receptor turnover.

Animals↗
PubMed1983

Effect of cycloheximide administration on bupivacaine-induced acute muscle degradation.

We have examined the effect of cycloheximide on bupivacaine-induced, macrophage-mediated muscle degeneration in rats and obtained the following results. Direct intramuscular injection of bupivacaine into soleus muscle caused uniform muscle degeneration (Ishiura, S. et al. (1983) J. Biochem. 94, 311-314). The degeneration was most prominent 48 h after injection, with many infiltrating macrophages. Intraperitoneal administration of cycloheximide prevented the bupivacaine-induced macrophage invasion and decrease of structural proteins 48 h after injection. Cycloheximide inhibited the increase in lysosomal enzymes in bupivacaine-treated muscle. The peritoneal macrophages increased in number immediately after bupivacaine injection, while cycloheximide inhibited their accumulation. These results indicated that cycloheximide inhibited muscle degradation by preventing macrophage proliferation.

Animals↗
PubMed1981

The effect of cycloheximide on synthesis of proteoglycans by cultured chondrocytes from the Swarm rat chondrosarcoma.

Proteoglycan synthesis by cultured chondrocytes from the Swarm rat chondrosarcoma was examined after treatment with 0.1 mg/ml of cycloheximide which inhibited [3H]serine incorporation into total protein by greater than 90%. Incorporation of [35S]sulfate into proteoglycans decreased with nearly first order kinetics (t 1/2 = 96 +/- 6 min) with an accompanying increase in the size of the proteoglycan molecules, primary due to an increase in chondroitin sulfate chain sizes. After 5 h of cycloheximide treatment, when [35S]sulfate incorporation was inhibited by about 90%, addition of 1 mM beta-D-xyloside restored 76% of the incorporation into chondroitin sulfate observed in cultures treated only with xyloside. This suggests that the biochemical pathways for the affected by cycloheximide treatment. Cultures were prelabeled for 15 min with either [3H]serine or [35S]-methionine, and then cycloheximide was added to block further protein synthesis. Both precursors appeared in completed proteoglycan molecules with nearly first order kinetics with t 1/2 values of 92 +/- 8 and 101 +/- 11 min for [3H]serine and [35S]methionine, respectively, values in close agreement with the t 1/2 from the [35S]sulfate data. These results suggest that after cycloheximide treatment, the rate of [35S]sulfate incorporation into proteoglycan, after a correction for increases in chondroitin sulfate chain size, was directly proportional to the size of the intracellular pool of core protein. From the steady state rate of proteoglycan synthesis (estimated to be about 80 ng/min/10(6) cells in separate experiments) and a corrected t 1/2 value of 60 min, the amount of precursor core protein can be calculated to be about 500 ng/10(6) cells in these experiments.

Animals↗
PubMedDate not supplied

[Nucleo-cytoplasmic mRNA transport in liver rat and hepatoma cells following suppression of protein synthesis by cycloheximide].

Specific radioactivity of uridylic nucleotide pool was found to be 2-2.5-fold higher in rat liver cells treated with cycloheximide within 3 hrs as compared with the control liver cells. Cycloheximide did not affect the specific radioactivity of the nucleotide pool in cells of Zajhdel ascites hepatoma. Nuclear-cytoplasmic transport of mRNA was decreased by 40-60% in rat liver cells after inhibition of protein synthesis by cycloheximide within 3 hrs. In this case, synthesis of non-ribosomal RNA was also decreased by 20-30% in nuclei. Treatment with cycloheximide caused 2.5-3-fold increase in synthesis of non-ribosomal nuclear RNA in rat cells of Zajhdel ascites hepatoma; amount of mRNA, transported from nucleus into cytoplasm, was also 2-3-fold higher in the tumoral cells as compared with controls. Under conditions of cycloheximide action, mRNA, which is transported from nuclei, continued to enter the polyribosomes of Zajhdel ascites hepatoma cells at the normal rate, although the protein synthesis did not occur in these polyribosomes.

Animals↗
PubMed1994

Effect of protein synthesis inhibition by cycloheximide on lymphocyte circulation.

BACKGROUND: Lymphocyte recirculation is directed by glycoprotein adhesion molecules on lymphocytes and endothelial cells of lymphoid tissues. Lymphocyte circulation in different lymphoid tissues is dependent on the type of glycoprotein adhesion molecules present. In the present study, the effects of inhibiting new protein synthesis on the ability of lymphocytes to circulate and home to different lymphoid tissues was investigated. EXPERIMENTAL DESIGN: New Zealand White rabbits and Lewis white rats were treated with cycloheximide or buffer. Total circulating lymphocyte counts and lymphocyte subsets were measured. Rabbits were given autologous, 111indium-labeled lymphocytes to determine if there were changes in the organ distribution of lymphocytes after cycloheximide treatment. RESULTS: After cycloheximide treatment, the number of circulating lymphocytes but not neutrophils increased significantly by 2 hours in both rabbits and rats. T cells, B cells, and L-selectin-positive lymphocytes showed similar increases. Measurements of the distribution of the radiolabeled, autologous lymphocytes in cycloheximide-treated animals showed significantly greater numbers circulating in the peripheral blood and decreased numbers in Peyer's patches, mesenteric lymph nodes, and spleens compared with controls. In contrast, the number of radiolabeled lymphocytes in the lung was not decreased after cycloheximide administration. CONCLUSIONS: These results indicate that protein synthesis inhibition causes lymphocytosis due to decreased lymphocyte homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This effect was not specific for distinct lymphocyte subsets, including T cells, B cells, or lymphocytes expressing L-selectin. These data show that molecules modulating lymphocyte homing in some organs have rapid turnover rates and suggest that changes in homing during the inflammatory process can be rapidly regulated by changes in protein translation.

Animals↗
PubMed1970

Specificity of cycloheximide in higher plant systems.

Although cycloheximide is extremely inhibitory to protein synthesis in vivo in higher plants, the reported insensitivity of some plant ribosomes suggests that it may not invariably act at the ribosomal level. This suggestion is reinforced by results obtained with red beet storage tissue disks, the respiration of which is stimulated by cycloheximide at 1 microgram per milliliter. Inorganic ion uptake by these disks is inhibited by cycloheximide at 1 microgram per milliliter while the uptake of organic compounds, by comparison, is unaffected. Ion uptake by all nongreen tissues tested is inhibited by cycloheximide, but leaf tissue is unaffected, indicating that the ion absorption mechanism in the leaf may differ fundamentally from that in the root. It is concluded that cycloheximide can affect cellular metabolism other than by inhibiting protein synthesis and that the inhibition of ion uptake may be due to disruption of the energy supply.

Journal Article↗
PubMed1990

Effects of cycloheximide on abscisic Acid biosynthesis and stomatal aperture in bean leaves.

Cycloheximide was shown to block abscisic acid (ABA) biosynthesis in nonstressed as well as in stressed Phaseolus vulgaris leaves. Leaf wilting caused by cycloheximide resulted from increased stomatal opening as judged by a decreased stomatal diffusion resistance. The inhibition of ABA biosynthesis by cycloheximide was at least partially responsible for the increase in stomatal opening as suggested by the cooccurrence of inhibition of ABA biosynthesis and increased stomatal opening, and the partial reversal of stomatal opening in cycloheximide-treated leaves by exogenous ABA. Dark treatment failed to close stomatal in cycloheximide-treated leaves, suggesting that stomatal closure in response to darkness may normally be mediated by ABA.

Journal Article↗
PubMed1980

Covalently closed circular DNAs of murine type C retrovirus: depressed formation in cells treated with cycloheximide early after infection.

Formation of viral closed circular supercoiled DNA duplexes and production of progeny virus were both inhibited in cultured mouse cells treated with cycloheximide in the first 4 h of type C retrovirus infection. With different doses of cycloheximide to cause different degrees of inhibition, the number of viral supercoiled DNA duplexes detected in the cells at 11 h showed an apparent correlation with the amount of progeny virus produced in the 12- to 22-h period of infection. A slight accumulation of the full-genome linear duplex and an open circular duplex of viral DNA intermediate was observed in the cycloheximide-treated cells. Cycloheximide given to the cells during the time of conversion of viral DNA from linear to supercoiled duplex forms (6 to 11 h after virus inoculation) did not inhibit the conversion. These kinetic data suggest that a cycloheximide-sensitive metabolic process, probably early viral protein synthesis, is required for retrovirus replication and supercoiled viral DNA formation in the cell.

Animals↗
PubMed1997

Rapid induction of Fas antigen mRNA expression in vivo by cycloheximide.

The effect of administration into rats of cycloheximide on the expression of genes, such as tissue transglutaminase, testosterone-repressed prostate message-2, Fas antigen, bcl-2, DNase I, and poly(ADP-ribose) polymerase, which were believed to be involved in the mechanism of apoptosis, was studied. While the effect of cycloheximide on the expression of genes other than Fas antigen was modest, only the expression of Fas antigen was elevated rapidly in most of the organs examined. A possible direct effect of cycloheximide on cells per se to induce Fas antigen mRNA expression was demonstrated by the tissue culture study using L929 fibroblast cells, although the magnitude of the induction detected in vitro was small compared with that in vivo. This induction of Fas antigen mRNA by cycloheximide is a first report on the modulation of Fas antigen mRNA expression in vivo.

Animals↗
PubMed1984

A cycloheximide-resistant pool of receptors for asialoglycoproteins and mannose 6-phosphate residues in the Golgi complex of hepatocytes.

Following in vivo administration of cycloheximide (20 mg/kg body weight i.p.) protein synthesis was completely inhibited (99%) in rat liver. No newly synthesized asialoglycoprotein receptor (ASGP-R) could be detected by metabolic labeling. Fluorescence immunocytochemistry of several secretory proteins and plasma membrane proteins, including the receptors for polymeric IgA (IgA-R), demonstrated a rapid loss from the Golgi complex following cycloheximide administration. On the other hand, two membrane proteins, the receptors for ASGP-R and mannose 6-phosphate (MP-R), were not altered in their cellular localization including the Golgi. Using quantitative immunoelectron microscopy with colloidal gold, we found that 2 h and 4 h after cycloheximide administration, the densities of ASGP-R and MP-R in the membranes of the Golgi complex were unaltered compared with control liver. Similarly, there was no significant effect of cycloheximide on the receptor labeling in coated vesicles and compartment of uncoupling receptors and ligands (CURL). These observations are consistent with an involvement of the Golgi and CURL pools of the receptors in intracellular trafficking, endocytosis and receptor recycling.

Animals↗