EFFECTS OF PROTEIN SYNTHESIS INHIBITORS ON ANGIOTENSIN-STIMULATED AND ANGIOTENSIN-INHIBITED FLUID TRANSPORT BY RAT JEJUNUM IN VIVO

1977 ◽  
Vol 74 (2) ◽  
pp. 213-221 ◽  
Author(s):  
JENNIFER E. BOLTON ◽  
K. A. MUNDAY ◽  
B. J. PARSONS
Keyword(s):  
Protein Synthesis ◽  
Fluid Transport ◽  
Actinomycin D ◽  
Inhibitory Response ◽  
Rat Jejunum ◽  
Protein Synthesis Inhibitors ◽  
Translation Stage ◽  
High Doses ◽  
Stimulation Of

A study has been made of the effects of protein synthesis inhibitors on the responses of rat jejunum in vivo to intravenous infusions of angiotensin. Actinomycin D, an inhibitor of the transcription stage of protein synthesis, was without effect on the stimulation of fluid transport which follows the infusion of low doses of angiotensin. Cycloheximide, an inhibitor of the translation stage of protein synthesis, blocked the stimulatory response to angiotensin, but was without effect on the inhibitory response to high doses of the hormone. It is concluded that low (physiological) doses of angiotensin stimulate fluid transport by a mechanism involving protein synthesis at a stage later than transcription whereas high doses of the hormone inhibit fluid transport by a process which does not require protein synthesis.

STUDIES ON THE MECHANISM OF ACTION OF ANGIOTENSIN ON FLUID TRANSPORT BY THE MUCOSA OF RAT DISTAL COLON

1972 ◽  
Vol 54 (3) ◽  
pp. 483-492 ◽  
Author(s):  
N. T. DAVIES ◽  
K. A. MUNDAY ◽  
B. J. PARSONS
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Rna Synthesis ◽  
Fluid Transport ◽  
Actinomycin D ◽  
Distal Colon ◽  
Rat Colon ◽  
Colon Mucosa ◽  
Rat Distal Colon ◽  
Stimulation Of

SUMMARY A study was made of the effects of cyclic AMP, theophylline, cycloheximide, puromycin and actinomycin D on the stimulation by angiotensin of fluid transport by sacs of rat colon mucosa. Cyclic AMP and theophylline, added together or separately, had no effect on fluid transport by colon sacs, suggesting that the stimulation of fluid transport after the application of angiotensin is not mediated through cyclic AMP. Cycloheximide and puromycin (used at concentrations which block colon protein synthesis by 50–90%) had no effect on fluid transport by control colon sacs, but completely blocked the stimulatory response of the colon to angiotensin. In contrast, actinomycin D (at a concentration which significantly inhibits RNA synthesis) did not affect fluid transport in control or angiotensin-stimulated colon sacs. The results are discussed in relation to the possibility that protein synthesis, at the stage of translation, is involved in the action of angiotensin on fluid transport by the colon.

scholarly journals Regulation of the synthesis of lutropin-induced protein in rat testis Leydig cells

1978 ◽  
Vol 170 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Felix H. A. Janszen ◽  
Brian A. Cooke ◽  
Maria J. A. Van Driel ◽  
Henk J. Van Der Molen
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Leydig Cells ◽  
Actinomycin D ◽  
Polyacrylamide Gel Electrophoresis ◽  
Phosphodiesterase Inhibitor ◽  
Dibutyryl Cyclic Amp ◽  
Rat Testis ◽  
Stimulation Of

The mechanism of action of lutropin on the stimulation of the synthesis of a specific lutropin-induced protein in rat testis Leydig cells was investigated. Lutropin-induced protein has a mol.wt. of approx. 21000 and is detected by labelling the Leydig-cell proteins with [35S]methionine, followed by separation by polyacrylamide-gel electrophoresis and radioautography of the dried gel. The incorporation of35S into lutropin-induced protein was used as an estimate for the synthesis of the protein. Incubation of Leydig cells with dibutyryl cyclic AMP or cholera toxin also resulted in the stimulation of synthesis of the protein. Synthesis of lutropin-induced protein, when maximally stimulated with 100ng of lutropin/ml, could not be stimulated further by addition of dibutyryl cyclic AMP. Addition of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, further increased synthesis of the protein in the presence of a submaximal dose of lutropin (10ng/ml) but not in the absence of lutropin or with maximal amounts of lutropin (100 and 1000ng/ml). Actinomycin D prevented the effect of lutropin on the stimulation of lutropin-induced protein synthesis when added immediately or 1h after the start of the incubation, but not when added after 5–6h. This is interpreted as reflecting that, after induction of mRNA coding for lutropin-induced protein, lutropin had no influence on the synthesis of the protein in the presence of actinomycin D. Synthesis of the protein was also stimulated in vivo by injection of choriogonadotropin into rats 1 day after hypophysectomy, and the time course of this stimulation of lutropin-induced protein synthesis in vivo was similar to that obtained by incubating Leydig cells in vitro with lutropin. From these results it is concluded that stimulation of lutropin-induced protein synthesis by lutropin is most probably mediated by cyclic AMP and involves synthesis of mRNA.

scholarly journals Corticotropin regulation of the synthesis of a specific rat adrenal cytosolic protein. Effects of hypophysectomy and actinomycin D

1979 ◽  
Vol 182 (3) ◽  
pp. 717-725 ◽  
Author(s):  
Alice Dazord ◽  
Dominique Gallet ◽  
Helene Cohen ◽  
Jose M. Saez
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Total Protein ◽  
Actinomycin D ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cytosolic Protein ◽  
And Control ◽  
Corticotropin Stimulation ◽  
Stimulation Of

The mechanism of corticotropin stimulation of the synthesis of a specific rat adrenal cytosolic protein was investigated. This protein (protein E) has a mol.wt. of approx. 30000. It is detected by polyacrylamide-gel electrophoresis of cytosol prepared from adrenal slices from rats treated with corticotropin in vivo and control rats, the slices being incubated with [3H]- and [14C]-leucine respectively. In rats 1–15 days after hypophysectomy, corticotropin, like dibutyryl cyclic AMP, induces an increase in protein E similar to that induced in control rats, even though both compounds no longer stimulate total protein synthesis. Corticotropin stimulation of protein E synthesis is mediated by cyclic AMP but not by corticosterone, since aminoglutethimide, a steroidogenic inhibitor, does not affect corticotropin stimulation, and dexamethasone alone has no effect. Actinomycin D, when injected in vivo 1h before or after corticotropin injection, prevents the effect of corticotropin on protein E synthesis, which is interpreted as evidence that mRNA synthesis is necessary for the stimulation of protein E synthesis. When injected more than 2h after corticotropin, actinomycin D does not prevent corticotropin stimulation of protein E synthesis, but completely blocks corticotropin stimulation of total protein synthesis. This is interpreted as meaning that, after stimulation of mRNA coding for protein E, corticotropin has no effect on the synthesis of protein E. On the other hand, corticotropin stimulation of protein E synthesis persists after hypophysectomy even though it no longer stimulates total protein synthesis. These data suggest that the factor(s) involved in the synthesis of protein E are more stable than those involved in total protein synthesis.

scholarly journals The breakdown of Tetrahymena ribosomes in vivo. The effects of inhibitors

1982 ◽  
Vol 208 (3) ◽  
pp. 831-837 ◽  
Author(s):  
H G Klemperer ◽  
D J Pilley
Keyword(s):  
Protein Synthesis ◽  
Energy Metabolism ◽  
Ribosomal Rna ◽  
Lysosomal Enzymes ◽  
Actinomycin D ◽  
Degradation Mechanism ◽  
Protein Synthesis Inhibitors ◽  
Total Rna

1. When Tetrahymena were deprived of nutrients 50% of the polysomes disaggregated within 20 min and 20% of the total RNA broke down in 2 h. Ribosomal RNA accounted for 75% of the RNA breakdown. 2. RNA labelled by a long incubation with [14C]uridine was stable in growing cells and in the presence of actinomycin D, but broke down at the same rate as bulk RNA in starved cells. 3. The following substances inhibited the loss of RNA during starvation: cycloheximide (which inhibited both polysome disaggregation and protein synthesis), inhibitors of energy metabolism and puromycin (all of which caused polysome disaggregation and inhibited protein synthesis), and chloroquine and 7-amino-1-chloro-3-L-tosylamidoheptan-2-one (‘TLCK’) (neither of which affected polysomes or protein synthesis). 4. Starvation appears to activate a ribosome degradation mechanism that may involve lysosomal and non-lysosomal enzymes.

scholarly journals Stimulation of Monocyte Procoagulant Activity by Adherence to Different Surfaces

1977 ◽  
Author(s):  
C.J.W. van Ginkel ◽  
J.I.H. Oh ◽  
W.G. van Aken ◽  
J. Vreeken
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
Procoagulant Activity ◽  
Adherent Cells ◽  
Protein Synthesis Inhibitors ◽  
Mononuclear Leukocyte ◽  
Thromboplastic Activity ◽  
Recalcification Time ◽  
Monocyte Adherence ◽  
Stimulation Of

When mononuclear leukocyte suspensions (5.109 cells/1, 25% monocytes) were incubated on glass dishes, 57 ± 1% of the monocytes were found to adhere to the surface after 3.5 h incubation at 37°C. It was found that the adherent cells shortened the recalcification time from 435 ± 35 to 50 + 2 sec using normal plasma as substrate. However, when monocyte adherence was prevented by incubating the leukocytes on cuprophane (3 + 1% adherence), much less PCA was detectable (the recalcification time was shortened from 435 ± 35 to 201 ± 19 sec). After exposing to glass the non-adherent monocytes had negligible PCA in comparison to the adherent monocytes. Protein synthesis inhibitors (cycloheximide and actinomycin D) inhibited PCA generation but did not affect monocyte adherence. These data provide the first evidence that adherence of monocytes is a stimulus for the generation of thromboplastic activity.

EFFECT OF ACTINOMYCIN D ON TSH-INDUCED STIMULATION OF THYROIDAL PROTEIN SYNTHESIS IN THE RAT

1974 ◽  
Vol 77 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Gustav Wägar
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
The Other ◽  
Leucine Incorporation ◽  
Short Term ◽  
Other Hand ◽  
Thyroid Glands ◽  
Translational Level ◽  
Stimulation Of

ABSTRACT Whether the short-term regulation of thyroidal protein synthesis by TSH occurs at the transcriptional or the translational level was tested by measuring the effect of actinomycin D (act D) on the TSH-induced stimulation of L-14C-leucine incorporation into the thyroidal proteins of rats. TSH was injected 6 h before the rats were killed. The thyroid glands were then removed and incubated in vitro in the presence of L-14C-leucine for 2 h. The pronounced stimulation of leucine incorporation in the TSH-treated animals was depressed as compared with controls but still significant even when the animals had been pre-treated with 100 μg act D 24 and 7 h before sacrifice. On the other hand, act D strongly decreased incorporation of 3H-uridine into RNA. Short-term regulation of thyroidal protein synthesis by TSH appears to be partly but not wholly dependent on neosynthesis of RNA. Hence regulation may partly occur at the translation level of protein synthesis.

Protein synthesis is required for rapid degradation of tubulin mRNA and other deflagellation-induced RNAs in Chlamydomonas reinhardi

1986 ◽  
Vol 6 (1) ◽  
pp. 54-61
Author(s):  
E J Baker ◽  
L R Keller ◽  
J A Schloss ◽  
J L Rosenbaum
Keyword(s):  
Protein Synthesis ◽  
Transcriptional Control ◽  
Protein S ◽  
Protein Synthesis Inhibitors ◽  
Control Factors ◽  
Flagellar Proteins ◽  
The Stability ◽  
And Control

After flagellar detachment in Chlamydomonas reinhardi, there is a rapid synthesis and accumulation of mRNAs for tubulin and other flagellar proteins. Maximum levels of these mRNAs (flagellar RNAs) are reached within 1 h after deflagellation, after which they are rapidly degraded to their predeflagellation levels. The degradation of alpha- and beta-tubulin RNAs was shown to be due to the shortening of their half-lives after accumulation (Baker et al., J. Cell Biol. 99:2074-2081, 1984). Deflagellation in the presence of protein synthesis inhibitors results in the accumulation of tubulin and other flagellar mRNAs by kinetics similar to those of controls. However, unlike controls, in which the accumulated mRNAs are rapidly degraded, these mRNAs are stabilized in cycloheximide. The stabilization by cycloheximide is specific for the flagellar mRNAs accumulated after deflagellation, since there is no change in the levels of flagellar mRNAs in nondeflagellated (uninduced) cells in the presence of cycloheximide. The kinetics of flagellar mRNA synthesis after deflagellation are shown to be the same in cycloheximide-treated and control cells by in vivo labeling and in vitro nuclear runoff experiments. These results show that protein synthesis is not required for the induced synthesis of flagellar mRNAs, and that all necessary transcriptional control factors are present in the cell before deflagellation, but that protein synthesis is required for the accelerated degradation of the accumulated flagellar mRNAs. Since cycloheximide prevents the induced synthesis and accumulation of flagellar proteins, it is possible that the product(s) of protein synthesis required for the accelerated decay of these mRNAs is a flagellar protein(s). The possibility that one or more flagellar proteins autoregulate the stability of the flagellar mRNAs is discussed.

scholarly journals Pharmacokinetic and Pharmacodynamic Evaluation of P-873 versus Klebsiella pneumoniae in a Neutropenic Murine Thigh Infection Model

2013 ◽  
Vol 57 (4) ◽  
pp. 1971-1973 ◽  
Author(s):  
Lucinda M. Lamb ◽  
Jared L. Crandon ◽  
David P. Nicolau
Keyword(s):  
Protein Synthesis ◽  
Klebsiella Pneumoniae ◽  
Infection Model ◽  
Protein Synthesis Inhibitors ◽  
Content Type ◽  
Pharmacokinetic Properties

ABSTRACTP-873 is a novel compound in the RX-04 pyrrolocytosine series of protein synthesis inhibitors currently under development by Rib-X Pharmaceuticals. We evaluated the pharmacodynamic and pharmacokinetic properties of this compound againstKlebsiella pneumoniaeusing a murine neutropenic thigh infection model. P-873 demonstrated potent and rapidin vivoactivity against this organism with enhanced penetration and duration of exposure in thigh tissue.

Stimulation of transport of alpha-aminoisobutyric acid into the testes of immature mice in vivo by follicle-stimulating hormone

1982 ◽  
Vol 100 (1) ◽  
pp. 137-142
Author(s):  
Nila Oza ◽  
Sarah J. Meanock ◽  
A. G. Davies
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Specific Activity ◽  
Follicle Stimulating Hormone ◽  
Acid Transport ◽  
Aminoisobutyric Acid ◽  
Old Mice ◽  
Stimulation Of

Abstract. Groups of immature mice were injected sc with radiocarbon-labelled alpha-aminoisobutyric acid (AIB) after being given a single sc injection of hFSH or of 0.9% saline. As an index of the transport of AIB, the specific activity of isotope was measured in homogenates of testis and of liver. FSH treatment caused statistically significant increases in the specific activity of isotope in the testes and in the ratio of testicular to liver specific activity. The effect was greatest in 9-day-old mice injected with FSH 16 h before removal of the testes. Uptake of labelled AIB was not stimulated after administration of hCG or testosterone. Doses of cycloheximide sufficient to reduce the rate of protein synthesis by over 99% did not impair testicular uptake of labelled AIB or the influence of FSH on AIB uptake. These results suggest that FSH stimulates amino acid transport into cells of the immature testis and that this action is independent of the stimulatory effect of FSH on testicular protein synthesis.

scholarly journals Poly(A) tail shortening is the translation-dependent step in c-myc mRNA degradation.

1990 ◽  
Vol 10 (12) ◽  
pp. 6132-6140 ◽  
Author(s):  
I A Laird-Offringa ◽  
C L de Wit ◽  
P Elfferich ◽  
A J van der Eb
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
Degradation Pathway ◽  
Mrna Degradation ◽  
The Body ◽  
Second Step ◽  
Protein Synthesis Inhibitors ◽  
Rapid Degradation ◽  
Translation Block ◽  
Insight Into

The highly unstable c-myc mRNA has been shown to be stabilized in cells treated with protein synthesis inhibitors. We have studied this phenomenon in an effort to gain more insight into the degradation pathway of this mRNA. Our results indicate that the stabilization of c-myc mRNA in the absence of translation can be fully explained by the inhibition of translation-dependent poly(A) tail shortening. This view is based on the following observations. First, the normally rapid shortening of the c-myc poly(A) tail was slowed down by a translation block. Second, c-myc messengers which carry a short poly(A) tail, as a result of prolonged actinomycin D or 3'-deoxyadenosine treatment, were not stabilized by the inhibition of translation. We propose that c-myc mRNA degradation proceeds in at least two steps. The first step is the shortening of long poly(A) tails. This step requires ongoing translation and thus is responsible for the delay in mRNA degradation observed in the presence of protein synthesis inhibitors. The second step involves rapid degradation of the body of the mRNA, possibly preceded by the removal of the short remainder of the poly(A) tail. This last step is independent of translation.

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