scholarly journals Circadian rhythm from the eye of Aplysia: temperature compensation of the effects of protein synthesis inhibitors

1980 ◽  
Vol 84 (1) ◽  
pp. 1-15
Author(s):  
J. W. Jacklet
Keyword(s):  
Protein Synthesis ◽  
Circadian Rhythm ◽  
Circadian Clock ◽  
Culture Medium ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Protein Synthesis Inhibitors ◽  
Response Curves ◽  
Synthesis Inhibitor ◽  
Maximum Phase

1. The circadian rhythm of compound action potentials (CAP) frequency recorded from the isolated eye of Aplysia in culture medium and darkness was subjected to step and pulse treatments with anisomycin, a protein synthesis inhibitor. 2. The step application of anisomycin and its continued presence in the culture medium lengthened the period of the rhythm in a dose-dependent manner. At 10(−8) M the period was increased from the normal 26.5 h to about 28 h and at 10(−7) M the period was lengthened to 31 h or longer. At 10(−6) M the rhythm was suppressed but the CAP activity continued without the cyclic variations in CAP frequency. 3. Six-hour pulses of anisomycin at 10(−6) M caused phase-dependent phase-shifts of the rhythm. Maximum phase delays of 15 h were obtained at CT (circadian time) 2 and maximum phase advances of 4 h were obtained at CT 6. The phase response curves at 12, 15 and 17 degrees C were essentially identical. 4. Anisomycin appears to act rather selectively on the circadian clock mechanism. It does not alter the CAP amplitude and duration and it does not alter the bursting pacemaker mechanism of the optic nerve CAP or central neurones. 5. The results support the hypothesis that the synthesis of a protein or polypeptide on eucaryotic ribosomes is an essential part of the circadian clock timing mechanism. The sensitivity of the clock to anisomycin is the same at three different temperatures (12, 15 and 17 degrees C) within the physiological range of temperatures for Aplysia, as expected for a clock whose period length is temperature compensated (Q10 1.02) over that same range. 6. At the critical phases of CT 1-4, anisomycin pulses often caused unusual perturbations of the rhythm. These effects are consistent with the hypothesis that the circadian rhythm is a multioscillator system.

Protein synthesis requirement of the Aplysia circadian clock. Tested by active and inactive derivatives of the inhibitor anisomycin

1980 ◽  
Vol 85 (1) ◽  
pp. 33-42
Author(s):  
J. W. Jacklet
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Compound Action Potential ◽  
Phase Shifts ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Inhibitor Molecule ◽  
Group 5 ◽  
Characteristic Effect ◽  
Derivatives Of

1.The circadian rhythm of compound action potential frequency recorded from the isolated eye of Aplysia in culture medium and darkness was subjected to 6 h pulse treatments with either anisomycin, a protein synthesis inhibitor, or inactive derivatives of anisomycin. 2. Anisomycin caused phase-dependent phase shifts of the rhythm as expected from previous experiments, but none of the derivative molecules caused phase shifts or perturbed the rhythm. 3. Anisomycin inhibited eye-protein synthesis by 75% at the concentrations (10(−6) M) used in the phase shifting experiments but none of the derivatives inhibited synthesis. 4. Only those molecules that actually inhibited protein synthesis caused phase shifts of the clock, although the inactive derivatives differed from anisomycin by only an acetyl group. 5. The results strengthen the conclusion that the inhibition of protein synthesis caused by anisomycin is important in perturbing the timing of the circadian clock and not some other characteristic effect of the inhibitor molecule. Together with the results from other systems, these findings imply that the daily synthesis of protein is a general requirement for circadian clocks.

scholarly journals ON THE MECHANISM OF ADAPTATION TO PROTEIN SYNTHESIS INHIBITORS BY TETRAHYMENA

1974 ◽  
Vol 62 (3) ◽  
pp. 707-716 ◽  
Author(s):  
Charles T. Roberts ◽  
Eduardo Orias
Keyword(s):  
Protein Synthesis ◽  
Cell Division ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Cellular Functions ◽  
Synthesis Inhibitor ◽  
Experimental Conditions ◽  
Cellular Machinery ◽  
Time Required ◽  
Sublethal Concentrations

Tetrahymena is able to adapt to the presence of sublethal concentrations of many drugs which inhibit a wide variety of cellular functions. In spite of the generality of this phenomenon in Tetrahymena, the mechanism of adaptation at the cellular and molecular levels is unknown. This study deals mainly with adaptation to the protein synthesis inhibitors, cycloheximide and emetine. The physiological response of Tetrahymena to sublethal concentrations of these drugs is an immediate cessation of cell division for a period of time dependent on the drug concentration, followed by an abrupt resumption of exponential growth at a constant rate. By measuring the length of the growth lags under a variety of experimental conditions, we have confirmed several observations made by Frankel and coworkers, and provide evidence for two new phenomena associated with adaptation to cycloheximide: (a) adaptation to cycloheximide also results in adaptation of cells to emetine, another protein synthesis inhibitor not closely related structurally to cycloheximide. We have termed this phenomenon cross adaptation, (b) exposure to concentrations of cycloheximide too low to cause any growth lags or inhibition of protein synthesis significantly shortens the time required by cells to adapt to higher concentrations of cycloheximide. We have termed this phenomenon facilitation. Facilitation shows some degree of specificity in that facilitation with cycloheximide has no effect on adaptation to emetine. From this, we infer the existence of two distinct systems involved in adaptation to cycloheximide, one of which shows a higher degree of specificity towards cycloheximide than the other. We also show that transfer of adapted or facilitated cells to drug-free medium results in a gradual but complete resensitization. The kinetics of resensitization suggest that the cellular machinery responsible for adaptation and facilitation does not leave the cell, but is simply diluted out during cell division.

scholarly journals Social Fear Memory Requires Two Stages of Protein Synthesis in Mice

2020 ◽  
Vol 21 (15) ◽  
pp. 5537
Author(s):  
Johannes Kornhuber ◽  
Iulia Zoicas
Keyword(s):  
Protein Synthesis ◽  
Temporal Dynamics ◽  
De Novo ◽  
Fear Memory ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Synthesis Inhibitor ◽  
Systemic Injection ◽  
Social Fear ◽  
Two Stages

It is well known that long-term consolidation of newly acquired information, including information related to social fear, require de novo protein synthesis. However, the temporal dynamics of protein synthesis during the consolidation of social fear memories is unclear. To address this question, mice received a single systemic injection with the protein synthesis inhibitor, anisomycin, at different time-points before or after social fear conditioning (SFC), and memory was assessed 24 h later. We showed that anisomycin impaired the consolidation of social fear memories in a time-point-dependent manner. Mice that received anisomycin 20 min before, immediately after, 6 h, or 8 h after SFC showed reduced expression of social fear, indicating impaired social fear memory, whereas anisomycin caused no effects when administered 4 h after SFC. These results suggest that consolidation of social fear memories requires two stages of protein synthesis: (1) an initial stage starting during or immediately after SFC, and (2) a second stage starting around 6 h after SFC and lasting for at least 5 h.

scholarly journals Signal transduction for chemotaxis and haptotaxis by matrix molecules in tumor cells.

1990 ◽  
Vol 110 (4) ◽  
pp. 1427-1438 ◽  
Author(s):  
S Aznavoorian ◽  
M L Stracke ◽  
H Krutzsch ◽  
E Schiffmann ◽  
L A Liotta
Keyword(s):  
Protein Synthesis ◽  
Matrix Protein ◽  
Type Iv Collagen ◽  
De Novo ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Recognition Sequence ◽  
Synthesis Inhibitor ◽  
Concentration Dependent Manner ◽  
Type Iv

Transduction of signals initiating motility by extracellular matrix (ECM) molecules differed depending on the type of matrix molecule and whether the ligand was in solution or bound to a substratum. Laminin, fibronectin, and type IV collagen stimulated both chemotaxis and haptotaxis of the A2058 human melanoma cell line. Peak chemotactic responses were reached at 50-200 nM for laminin, 50-100 nM for fibronectin, and 200-370 nM for type IV collagen. Checkerboard analysis of each attractant in solution demonstrated a predominantly directional (chemotactic) response, with a minor chemokinetic component. The cells also migrated in a concentration-dependent manner to insoluble step gradients of substratum-bound attractant (haptotaxis). The haptotactic responses reached maximal levels at coating concentrations of 20 nM for laminin and type IV collagen, and from 30 to 45 nM for fibronectin. Pretreatment of cells with the protein synthesis inhibitor, cycloheximide (5 micrograms/ml), resulted in a 5-30% inhibition of both chemotactic and haptotactic responses to each matrix protein, indicating that de novo protein synthesis was not required for a significant motility response. Pretreatment of cells with 50-500 micrograms/ml of synthetic peptides containing the fibronectin cell-recognition sequence GRGDS resulted in a concentration-dependent inhibition of fibronectin-mediated chemotaxis and haptotaxis (70-80% inhibition compared to control motility); negative control peptide GRGES had only a minimal effect. Neither GRGDS nor GRGES significantly inhibited motility to laminin or type IV collagen. Therefore, these results support a role for the RGD-directed integrin receptor in both types of motility response to fibronectin. After pretreatment with pertussis toxin (PT), chemotactic responses to laminin, fibronectin, and type IV collagen were distinctly different. Chemotaxis to laminin was intermediate in sensitivity; chemotaxis to fibronectin was completely insensitive; and chemotaxis to type IV collagen was profoundly inhibited by PT. In marked contrast to the inhibition of chemotaxis, the hepatotactic responses to all three ligands were unaffected by any of the tested concentrations of PT. High concentrations of cholera toxin (CT; 10 micrograms/ml) or the cAMP analogue, 8-Br-cAMP (0.5 mM), did not significantly affect chemotactic or haptotactic motility to any of the attractant proteins, ruling out the involvement of cAMP in the biochemical pathway initiating motility in these cells. The sensitivity of chemotaxis induced by laminin and type IV collagen, but not fibronectin, to PT indicates the involvement of a PT-sensitive G protein in transduction of the signals initiating motility to soluble laminin and type IV collagen.(ABSTRACT TRUNCATED AT 400 WORDS)

Drug inhibition of memory formation in chickens II. Short-term memory

1971 ◽  
Vol 178 (1053) ◽  
pp. 455-464 ◽  
Keyword(s):  
Protein Synthesis ◽  
Sodium Pump ◽  
Short Term Memory ◽  
Memory Loss ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Short Term ◽  
Synthesis Inhibitor ◽  
Term Memory

1. Memory in day-old-chickens during the first few hours after learning can be made to decline by the prior intracranial injection of two classes of drugs. 2. Sodium pump inhibitors in increasing doses cause increasingly rapid loss of memory. 3. Protein synthesis inhibitors in increasing doses attain a maximum potency in causing memory decline and the rate may not be further accelerated by higher doses. 4. Adding a sodium pump inhibitor to the inhibition of protein synthesis increases memory loss. 5. Adding a protein synthesis inhibitor to a sodium pump inhibitor causes no further loss. 6. Therefore within a few minutes of learning a short-term memory of limited time span but independent of protein synthesis becomes supplemented and eventually replaced by a long-term storage requiring protein synthesis. The amount of long-term store is set by the amount of short-term memory. 7. The short-term store could be directly dependent on post-activation enhancement of Na + extrusion from neurons. Some physiological mechanisms by which this could be achieved and how this might activate protein synthesis are discussed.

scholarly journals Evidence for Different Contributions of Archaea and Bacteria to the Ammonia-Oxidizing Potential of Diverse Oregon Soils

2010 ◽  
Vol 76 (23) ◽  
pp. 7691-7698 ◽  
Author(s):  
Anne E. Taylor ◽  
Lydia H. Zeglin ◽  
Sandra Dooley ◽  
David D. Myrold ◽  
Peter J. Bottomley
Keyword(s):  
Protein Synthesis ◽  
Protein Synthesis Inhibitor ◽  
Ammonia Oxidizing Bacteria ◽  
Ammonia Monooxygenase ◽  
Bacterial Protein ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibitor ◽  
Ammonia Oxidizing Archaea ◽  
Pasture Soil ◽  
Bacterial Protein Synthesis

ABSTRACT A method was developed to determine the contributions of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) to the nitrification potentials (NPs) of soils taken from forest, pasture, cropped, and fallowed (19 years) lands. Soil slurries were exposed to acetylene to irreversibly inactivate ammonia monooxygenase, and upon the removal of acetylene, the recovery of nitrification potential (RNP) was monitored in the presence and absence of bacterial or eukaryotic protein synthesis inhibitors. For unknown reasons, and despite measureable NPs, RNP did not occur consistently in forest soil samples; however, pasture, cropped, and fallowed soil RNPs commenced after lags that ranged from 12 to 30 h after acetylene removal. Cropped soil RNP was completely prevented by the bacterial protein synthesis inhibitor kanamycin (800 μg/ml), whereas a combination of kanamycin plus gentamicin (800 μg/ml each) only partially prevented the RNP (60%) of fallowed soils. Pasture soil RNP was completely insensitive to either kanamycin, gentamicin, or a combination of the two. Unlike cropped soil, pasture and fallowed soil RNPs occurred at both 30�C and 40�C and without supplemental NH4 + (≤10 μM NH4 + in solution), and pasture soil RNP demonstrated ∼50% insensitivity to 100 μM allyl thiourea (ATU). In addition, fallowed and pasture soil RNPs were insensitive to the fungal inhibitors nystatin and azoxystrobin. This combination of properties suggests that neither fungi nor AOB contributed to pasture soil RNP and that AOA were responsible for the RNP of the pasture soils. Both AOA and AOB may contribute to RNP in fallowed soil, while RNP in cropped soils was dominated by AOB.

scholarly journals Experience-specific anterograde amnesia: memory reacquisition deficit phenomenon and its characterization in the vertebrate learning model

2018 ◽  
Author(s):  
A. A. Tiunova ◽  
D. V. Bezryadnov ◽  
D.R. Gaeva ◽  
V.S. Solodovnikov ◽  
K.V. Anokhin
Keyword(s):  
Protein Synthesis ◽  
Nmda Receptor ◽  
Conditioned Avoidance ◽  
Anterograde Amnesia ◽  
Nmda Receptor Antagonist ◽  
Protein Synthesis Inhibitor ◽  
Avoidance Task ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibitor ◽  
Specific Memory

AbstractA common assumption from experiments that interfere with memory consolidation is that the resultant amnesia returns the brain of an animal to a tabula rasa state with respect to disturbed experience. However, recent studies in terrestrial snail classical conditioning revealed an odd phenomenon: animals were unable to relearn conditioned avoidance of specific food after this memory had been impaired by protein-synthesis inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists. Here we examined whether such specific memory reacquisition deficit can also be observed in vertebrate learning. We trained day-old chicks in a one-trial passive avoidance task by presenting them a bead of a specific color covered with a repellent substance, methyl anthranilate. Training was preceded by administration of the protein synthesis inhibitor anisomycin or the NMDA receptor antagonist MK-801. Both drugs produced permanent amnesia, and no spontaneous recovery of memory was observed. A second training was given to the amnestic animals either using a bead of the same color (retraining) or a new color (novel training). The interval between the first and second training was 2 or 24 h, and the retention test was given from 30 min to 48 h after the second training. Retraining of the amnestic chicks with the bead that was presented during the initial training failed to produce new avoidance memory for this stimulus at all the between-training and training-to-test intervals. This memory reacquisition deficit was specific and was not transferred to a new conditioned stimulus, which was readily learned. We suggest that such pharmacologically induced experience-specific anterograde amnesia might reflect general properties of normal memory allocation, and we discuss its possible neural bases.

Baculovirus ACMNPV as well as RNA- and protein-synthesis inhibitors induce apoptosis in a continuous midgut cell line, FPMI-CF-203, of Choristonuera fumiferana (Lepitoptera: tortricidae)

1995 ◽  
Vol 53 ◽  
pp. 1030-1031
Author(s):  
A.J. Brownwright ◽  
S.R. Palli ◽  
G.F. Caputo ◽  
S.S. Sohi
Keyword(s):  
Protein Synthesis ◽  
Nuclear Polyhedrosis Virus ◽  
Choristoneura Fumiferana ◽  
Protein Synthesis Inhibitor ◽  
Post Inoculation ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibitor ◽  
Successful Infection ◽  
Polyhedrosis Virus ◽  
Nuclear Polyhedrosis

Apoptosis is an active cellular self-destruction regulated by expression or repression of certain genes. Apoptosis can be caused by a variety of both external and internal stimuli. Whether these different stimuli that can cause apoptosis converge into a final pathway that leads to self-destruction is not known. This paper compares apoptosis caused by a baculovirus, an RNA-synthesis inhibitor and a protein-synthesis inhibitor.Inoculation of IPLB-SF-21 (SF-21) and FPMI-CF-203 (CF-203, Fig. 1, ) cells with Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV) and Choristoneura fumiferana multicapsid nuclear polyhedrosis virus (CfMNPV), respectively, results in successful infection as visualized by formation of occlusion bodies (OBs). However, inoculation of CF-203 cells with AcMNPV, or SF-21 cells with CFMNPV, is unsuccessful and no OBs are seen. Inoculation of CF-203 cells with AcMNPV results in premature lysis of cells beginning at 12 hr post-inoculation (pi) and most of the cells are lysed by 48 hr pi.

scholarly journals Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase

2016 ◽  
Vol 60 (10) ◽  
pp. 6271-6280 ◽  
Author(s):  
Andrés Palencia ◽  
Xianfeng Li ◽  
Wei Bu ◽  
Wai Choi ◽  
Charles Z. Ding ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mycobacterium Tuberculosis ◽  
Cell Activity ◽  
Trna Synthetase ◽  
Protein Synthesis Inhibitor ◽  
Drug Resistant ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibitor ◽  
Content Type

ABSTRACTThe recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains ofMycobacterium tuberculosishighlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective againstM. tuberculosisin TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), toM. tuberculosisLeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity againstM. tuberculosis. Importantly, their good oral bioavailability translates intoin vivoefficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.

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