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At least 19 recordsLinked to original sources
PubMedDate not supplied

Recovery of memory in chicks after disruption during learning: the reversibility of amnesia induced by protein synthesis inhibitors.

Protein synthesis inhibitors given during learning are known to disrupt memory in various animal species in several models of learning. However, there are suggestions that amnesia induced by protein synthesis inhibitors is not permanent--memory can be recovered by a reminder procedure, i.e., by presenting the animal with one of the components of the external environment which was part of the learning situation. The aim of the present work was to determine the existence of the reminder phenomenon in a well-studied model of single-session training to passive avoidance in chicks. Cycloheximide and anisomycin were used to induce amnesia. Reminder was performed using the aversive taste of methylanthranilate 24 h after training, and testing was conducted 48 h after training. The results obtained provide evidence that memory disrupted by protein synthesis inhibitors in chicks can be recovered by the reminder procedure.

Amnesia↗
PubMed1978

Induction of hepatic tyrosine aminotransferase mRNA by protein synthesis inhibitors.

Several protein synthesis inhibitors were as effective as the inducers hydrocortisone or cyclic AMP in elevating rat liver tyrosine aminotransferase mRNA levels when assayed in the wheat germ cell-free translational system. Cycloheximide, emetine, or puromycin increased this mRNA activity 6- to 7-fold within 4 h after in vivo administration. No increase in total hepatic mRNA levels or tryptophan oxygenase mRNA was found after treatment with these protein synthesis inhibitors. Furthermesults suggest that a short lived protein may specifically regulate the level of functional hepatic tyrosine aminotransferase mRNA or that ongoing translation of this mRNA is required for its degradation.

Animals↗
PubMed2001

Effects of indomethacin, NS-398 (a selective prostaglandin H synthase-2 inhibitor) and protein synthesis inhibitors on prostaglandin production by the guinea-pig placenta.

The outputs of PGF(2 alpha), PGE2 and 6-keto-PGF(1 alpha)were similar from the day 22 guinea-pig placenta and sub-placenta in culture, except for PGE2 output from the sub-placenta which was lower. Between days 22 and 29 of pregnancy, the outputs of PGF(2 alpha), PGE2 and 6-keto-PGF(1 alpha)during the initial 2 h culture period increased 6.9-, 1.1- and 3.2-fold, respectively, from the placenta, and 2.1-, 1.4- and 2.2-fold, respectively, from the sub-placenta. Therefore, there was a relatively specific increase in PGF(2 alpha)production by the guinea-pig placenta between days 22 and 29 of pregnancy. The output of PGFM from the cultured placenta also increased between days 22 and 29, indicating that the increase in PGF(2 alpha)output was due to increased synthesis rather than to decreased metabolism. By comparing the amounts of prostaglandins produced by tissue homogenates during a 1 h incubation period, it appears that there is approximately a 2-fold increase in the amount of prostaglandin H synthase (PGHS) present in the guinea-pig placenta between days 22 and 29. NS-398 (a specific inhibitor of PGHS-2) and indomethacin (an inhibitor of both PGHS-1 and PGHS-2) both inhibited prostaglandin production by homogenates of day 22 and day 29 placenta. Indomethacin was more effective than NS-398, except for their actions on PGF(2 alpha)production by the day 29 placenta where indomethacin and NS-398 were equiactive. Indomethacin and NS-398 were both very effective at inhibiting the outputs of PGF(2 alpha), PGE2 and 6-keto-PGF(1 alpha)from the day 22 and day 29 placenta and sub-placenta in culture, indicating that prostaglandin production by the guinea-pig placenta and sub-placenta in culture is largely dependent upon the activity of PGHS-2. The high production of PGF(2 alpha)by the day 29 placenta is not dependent on the continual synthesis of fresh protein(s), as inhibitors of protein synthesis did not reduce PGF(2 alpha)output from the day 29 guinea-pig placenta in culture.

Animals↗
PubMed1993

[Effects of protease inhibitors and protein synthesis inhibitors on cartilage tissue-dependent bone resorption].

We studied bone resorption of fetal rat femora in association with cartilage tissue. Some protease inhibitors, e.g., E-64, pepstatin A, phosphoramidon, amastatin, bestatin, foroxymithine, did not influence the bone resorption, but some serine protease inhibitors such as PMSF, TLCK, TPCK and elastatinal inhibited the bone resorption at 10(-5) M, 10(-4) M, 10(-4) M, 10(-4) M, respectively. A conditioned medium, obtained from cartilage tissue-cultured medium in the presence of 10(-4) M TPCK, which was then excluded from the medium by dialysis after the culture, stimulated the bone resorption. Cycloheximide (0.1 to 10 micrograms/ml) and puromycin (0.3 to 30 micrograms/ml) inhibited the cartilage tissue-dependent bone resorption. A A transient treatment of the femora with cycloheximide (3 micrograms/ml) for a day inhibited the bone resorption, but after the treatment, in the absence of cycloheximide, the femora gradually recovered the bone-resorbing activity. The conditioned medium, obtained from cartilage tissue-cultured medium in the presence of cycloheximide (3 micrograms/ml), which was then excluded from the medium by dialysis after the culture, failed to influence the bone resorption. These findings collectively suggest that cartilage tissue produces a bone resorption-stimulating factor(s) which is a serine protease or contains the protein as an inactive, latent form and then a certain serine protease converts it to an active form.

Animals↗
PubMed1974

Production of membrane whorls in rat liver by some inhibitors of protein synthesis.

Inhibitors of protein synthesis capable of differential effects on nascent peptide synthesis on membrane-bound and free polyribosomes were employed to investigate the structure and function of cellular membranes of liver. The formation of membranous whorls in the cytoplasm and distension of nuclear membranes were induced by inhibitors of protein synthesis (i.e., cycloheximide and emetine) which predominantly interfere with nascent peptide synthesis on membrane-bound polyribosomes in situ. Other inhibitors of protein synthesis such as puromycin and fusidic acid, which inhibit nascent peptide synthesis on both free and membrane-bound polyribosomes, and chloramphenicol, which inhibits mitochondrial protein synthesis, did not induce these alterations. Cycloheximide, puromycin, and chloramphenicol produce some common cellular lesions as reflected by similar alterations in morphology, such as swelling of mitochondria, degranulation of rough endoplasmic reticulum, and aggregation of free ribosomes. The process of whorl formation in the cytoplasm, the incorporation of [(3)H]leucine and of [(3)H]choline into endoplasmic reticulum and the total NADPH-cytochrome c reductase activity of the endoplasmic reticulum were determined. During maximum formation of membranous whorls, [(3)H]leucine incorporation into cytoplasmic membranes was inhibited, while [(3)H]choline incorporation into these structures was increased; maximum inhibition of protein synthesis and stimulation of choline incorporation into endoplasmic reticulum, however, preceded whorl formation. Cycloheximide decreased the activity of NADPH-cytochrome c reductase of rough endoplasmic reticulum, but increased NADPH-cytochrome c reductase activity of smooth endoplasmic reticulum. In addition, cycloheximide decreased the content of hemoprotein in both the microsomal and mitochondrial fractions of rat liver, and the activities of mixed function oxidase and of oxidative phosphorylation were impaired to different degrees. Succinate-stimulated microsomal oxidation was also inhibited. The possible mechanisms involved in the formation of membranous whorls, as well as their functions, are discussed.

Animals↗
PubMed1980

A comparison of the effects of localized brain administration of catecholamine and protein synthesis inhibitors on memory processing.

Protein synthesis inhibitors disrupt biosynthetic processes thought to control the formation of long-term memory. While the agents used (i.e. puromycin, acetoxycycloheximide, cycloheximide and anisomycin) do not selectively inhibit the synthesis of any particular class of protein, it has generally been hypothesized or assumed that the critical proteins(s) is structural and necessary for modification and/or growth of synapses. Recent reports indicated that all of the protein synthesis inhibitors causing amnesia inhibited tyrosine hydroxylase activity. Tyrosine hydroxylase is needed for the conversion of tyrosine to dopamine (DA) and norpinephrine (NE); altering the level of this enzyme could affect catecholamine (CA) turnover. Since drugs known to inhibit CA synthesis cause amnesia, it is of considerable interest whether amnesia induced by protein synthesis inhibitors depends basically on inhibition of CA synthesis.

Afferent Pathways↗
PubMed1980

Suppression of fever in rabbits by a protein synthesis inhibitor, anisomycin.

1. The protein synthesis inhibitor, anisomycin, was given into the cerebral ventricles of rabbits as a priming dose followed by a continuous infusion. Doses of 100, 200 and 300 microgram followed by infusions at 100, 200 and 300 microgram/hr inhibited the incorporation of [14C] leucine into hypothalamic protein by over 90%. 2. Injection and infusion of anisomycin (300 microgram) suppressed the febrile response to leucocyte (endogenous) pyrogen given into the ventricles (I.C.V.) or I.V. 3. Dialysis experiments showed that anisomycin did not combine irreversibly with leucocyte pyrogen. 4. Anisomycin did not interfere with thermoregulation in a cold environment. 5. It is concluded that pyrogenesis may involve a step which is dependent on synthesis of hypothalamic protein with a rapid turnover.

Animals↗
PubMed1995

Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1.

Inhibitors of protein synthesis, such as anisomycin and cycloheximide, lead to superinduction of immediate-early genes. We demonstrate that these two drugs activate intracellular signaling pathways involving both the mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) cascades. The activation of either pathway correlates with phosphorylation of the c-fos regulatory transcription factor Elk-1. In HeLa cells, anisomycin stabilizes c-fos mRNA when protein synthesis is inhibited to only 50%. Under these conditions, anisomycin, in contrast to cycloheximide, rapidly induces kinase activation and efficient Elk-1 phosphorylation. However, full inhibition of translation by either drug leads to prolonged activation of SAPK activity, while MAPK induction is transient. This correlates with prolonged Elk-1 phosphorylation and c-fos transcription. Elk-1 induction and c-fos activation are also observed in KB cells, in which anisomycin strongly induces SAPKs but not MAPKs. Purified p54 SAPK alpha efficiently phosphorylates the Elk-1 C-terminal domain in vitro and comigrates with anisomycin-activated kinases in in-gel kinase assays. Thus, Elk-1 provides a potential convergence point for the MAPK and SAPK signaling pathways. The activation of signal cascades and control of transcription factor function therefore represent prominent processes in immediate-early gene superinduction.

Anisomycin↗
PubMed1994

Inhibition of histamine release from RBL-2H3 cells by protein synthesis inhibitors.

Effects of cycloheximide, an inhibitor of protein synthesis, on histamine release from RBL-2H3 cells were examined. RBL-2H3 cells sensitized by rat antiserum to ascaris extract were challenged by the antigen, and histamine release during a period of 30 min was measured. Pretreatment with cycloheximide (1 microgram/ml) for 1 h significantly inhibited the antigen-induced histamine release (36% inhibition). The cycloheximide-induced inhibition of histamine release was abolished when the cells were further incubated in the absence of cycloheximide for 2 h. Pretreatment with puromycin (3 and 10 micrograms/ml), an inhibitor of protein synthesis, or actinomycin D (0.1-1 microgram/ml), an inhibitor of DNA-dependent RNA synthesis, also inhibited the antigen-induced histamine release in a concentration-dependent manner. Both ionomycin- and thapsigargin-induced histamine release were also inhibited by pretreatment with cycloheximide. Measurement of intracellular Ca2+ levels using quin 2 revealed that cycloheximide inhibits the increase in Ca2+ levels induced by the antigen, ionomycin or thapsigargin. These results suggest that histamine release induced by the antigen, ionomycin and thapsigargin in RBL-2H3 cells is mediated by protein(s) which is newly synthesized and inactivated rapidly, and the newly synthesized protein(s) is involved in the increase of intracellular Ca2+ levels induced by these stimulants.

Animals↗
PubMed1984

Effect of hemin and heme synthesis inhibitors on cellular protein synthesis.

Inhibitors of heme synthesis, 2,2'-bipyridyl, isonicotinic acid hydrazide (INH), and D,L-penicillamine markedly inhibited only the synthesis of hemoglobin and had no effect on the synthesis of the bulk of nonhemoglobin proteins in spleen cells of anemic mice. Exogenous hemin stimulated the synthesis of hemoglobin as well as the synthesis of the bulk of nonhemoglobin proteins. However, by further analysis of nonhemoglobin proteins it was possible to detect intermediates of hemoglobin synthesis, globin chains with highly specific radioactivity of L-[4,5-3H]leucine which were eluted together with nonhemoglobin proteins during the chromatography on CM-Sephadex C-50. Protein synthesis in Friend erythroleukemia cells of the Fw line which have the genetic defect of heme synthesis was resistant to D,L-penicillamine and Desferal; 2,2'-bipyridyl had an inhibitory effect. Hemin was without effect on protein synthesis in these neoplastic cells.

2,2'-Dipyridyl↗
PubMed1984

Apparent increases in phospholipid degradation and turnover during combined treatment with protein synthesis inhibitors and adrenocorticotropin.

Inhibitors of protein synthesis, cycloheximide and puromycin, blocked ACTH (adrenocorticotropin)-induced increases in phospholipid mass, including phosphatidylinositol, but paradoxically increase 32P-labelling (but not [3H]glycerol-labelling) therein. Cycloheximide also provoked an initial rapid decrease in 32P-prelabelled phospholipids, followed by an increase in [32P]Pi incorporation. These effects of cycloheximide and puromycin occurred in ACTH-treated (but not in control) cells. It appears that inhibition of protein synthesis during ACTH action provokes an increase in phospholipid degradation, followed by partial resynthesis of the phospholipid head groups.

Adrenocorticotropic Hormone↗
PubMed1977

Neuronal circadian rhythm: phase shifting by a protein synthesis inhibitor.

A potent inhibitor of protein synthesis, anisomycin, was applied (10(-6)M) in 6-hour pulses at specific phases in the circadian rhythm of endogenous compound action potential (CAP) activity recorded from the eye of Aplysia in vitro. The phase of the circadian rhythm was systematically advanced or delayed (up to 15 hours) depending on the specific phase at which the pulse was applied. The resultant phase response curve implicates protein synthesis on the eukaryotic ribosome as a fundamental part of the controlling processes that constitutes the circadian clock.

Action Potentials↗
PubMed1982

Effects of cycloheximide, a protein synthesis inhibitor, on mouse brain catecholamine biochemistry.

Cycloheximide (CXM), a protein synthesis inhibitor, has been shown to result in a marked inhibition of central catecholamine (CA) synthetic mechanisms at doses that cause amnesia in animals. Unlike other inhibitors of CA synthesis no significant depletion of whole brain NE or DA concentrations was observed 0.75, 1, 2, 3, 4, 6, 17, or 24 hours after administration of CXM (120 mg/kg) to C57BL/6J mice. In order to investigate the underlying basis of maintenance of CA levels in face of CA synthesis inhibition, the effects of CXM on in vitro release of 3H-NE was studied in mouse hypothalamic slices. CXM, in a dose related manner, significantly inhibited the potassium stimulated release of NE from hypothalamic slices. Anisomycin, another protein synthesis inhibitor, similarly inhibited NE release. These studies further document the effects of protein synthesis inhibitors on CA mechanisms and suggest that disruption of CA biochemistry may play a role in the amnesia observed after administration of protein synthesis inhibitors.

Animals↗
PubMed1989

Damage to protein synthesis concurrent with lipid peroxidation in rat liver slices: effect of halogenated compounds, peroxides, and vitamin E1.

Protein synthesis and lipid peroxidation were evaluated in rat liver slices incubated in the presence of oxidants and protein synthesis inhibitors. Protein synthesis by rat liver slices was evaluated by [3H]leucine incorporation into the trichloroacetic acid (TCA)-insoluble material, and lipid peroxidation was evaluated by thiobarbituric acid-reactive substances (TBARS) released into the incubation medium. Protein synthesis inhibition by bromotrichloromethane (BrCCl3) or t-butyl hydroperoxide (t-BOOH) depended on the incubation time and oxidant concentration. [3H]Leucine incorporation was decreased to 20 and 47% of control values and TBARS were enhanced from the control value of 16.9 to 45.3 and 62.5 nmol/g of liver by incubation for 1 h with 1 mM BrCCl3 and t-BOOH, respectively. Following incubation, both protein synthesis damage and lipid peroxidation were decreased in control and oxidant-treated slices prepared from rats injected with 200 mg of DL-alpha-tocopherol/kg of body wt. Release of lactate dehydrogenase was not enhanced by oxidant treatment. Protein synthesis inhibitors reversibly decreased [3H]leucine incorporation, but the effect of oxidants on protein synthesis was irreversible. Cumene hydroperoxide and methyl ethyl ketone peroxide, but not hydrogen peroxide, damaged protein synthesis and induced lipid peroxidation. The ability of carbon tetrabromide, benzyl chloride, bromoform, bromobenzene, carbon tetrachloride, chloroform, dichloromethane, and bromochloromethane to inhibit protein synthesis was correlated with their ability to induce lipid peroxidation, and with their LD50. The results suggest that oxidant-induced lipid peroxidation and protein synthesis damage occurred concurrently, and that protein synthesis inhibition may be involved in cell injury or death mediated by free radicals.

Animals↗
PubMed1983

Solubilization of a protein synthesis inhibitor from vaccinia virions.

The protein synthesis inhibitor previously demonstrated to be associated with vaccinia cores was quantitatively solubilized from vaccinia virions or cores after an endogenous protein kinase reaction at pH 10. The presence of the inhibitor in the soluble extract correlated with the presence of soluble virion proteins phosphorylated in vitro. Partially purified inhibitor blocked methionyl-tRNAfMet-40S initiation complex formation, as was the case in cell-free extracts derived from vaccinia virus-infected cells.

Hydrogen-Ion Concentration↗
PubMed1985

Defective assembly of the mitochondrial ribosomes in yeast cells grown in the presence of mitochondrial protein synthesis inhibitors.

The involvement of mitochondrial protein synthesis in the assembly of the mitochondrial ribosomes was investigated by studying the extent to which the assembly process can proceed in the presence of mitochondrial protein synthesis inhibitors erythromycin and chloramphenicol. Yeast cells grown in the presence of erythromycin (2 mg/ml) do not appear to contain any detectable amounts of the mitochondrial small (37 S) ribosomal subunit. Instead, a ribonucleoparticle with a sedimentation coefficient of 30 S was observed; this particle could be shown to be related to the mitochondrial small ribosomal subunit by two-dimensional gel electrophoretic analysis of its protein components. Since the var1 protein is the only mitochondrial translation product known to be associated with the mitochondrial ribosome, our results suggest that this protein is essential for the assembly of the mature small subunit, and that the var1 protein enters the pathway for the assembly of the small subunit at a late step. In at least one strain of yeast the accumulation of the 30-S particle appears to be very sensitive to catabolite repression. When yeast cells are grown in the presence of chloramphenicol instead of erythromycin, assembly of the small subunit appears to be only partially inhibited, and the presence of the 30-S particle could not be clearly demonstrated. This observation is consistent with the fact that in yeast, chloramphenicol inhibits mitochondrial protein synthesis by about 95% only and that the synthesis of the var1 protein appears to be the least sensitive to this inhibition.

Cell Fractionation↗
PubMed1991

Augmentation of monocyte-mediated antibody-dependent cellular cytotoxicity by protein synthesis inhibitors: evidence for an endogenous regulatory mechanism.

Protein synthesis inhibitors, cycloheximide and puromycin, were used in cytotoxic assays employing human peripheral blood monocytes as effectors and sheep erythrocytes as target cells. ADCC could be initiated and could also achieve its full lytic activity in the absence of new protein synthesis. Furthermore, an augmentation of ADCC was observed in the presence of protein synthesis inhibitors. This augmentation was due to an increase in the cytotoxic ability of effector cells rather than a change in the lytic susceptibility of the target. Enhanced cytotoxic potential could not be attributed to an increase in the expression of FcRI but could be due to increased availability of antibody for mediating ADCC as a result of reduced numbers of FcRII. Suppression of prostaglandin-E2 release by monocytes was noted in the presence of cycloheximide, possibly as a result of inhibition of synthesis of cyclooxygenase. However, prostaglandin-E2 and other arachidonic acid metabolites did not appear likely to play a role in negatively regulating human monocyte ADCC since neither cytotoxicity nor cycloheximide-induced augmentation was affected by the presence of exogenous prostaglandin-E2 or arachidonic acid. Cycloheximide was found to induce the secretion of superoxide anions by monocytes, but a role for reactive oxygen species in cycloheximide-induced augmentation of ADCC could not be established by experiments involving the use of catalase or superoxide dismutase. These results raise the possibility that a rapidly turning over protein which negatively regulates monocyte-mediated ADCC exists.

Antibody-Dependent Cell Cytotoxicity↗