A Comparison of the Effects of Endotoxin Upon Fibroblast Proliferation and Macromolecular Syntheses

1979 ◽  
Vol 58 (6) ◽  
pp. 1634-1639 ◽  
Author(s):  
R.E. Singer ◽  
W.G. Dutton
Keyword(s):  
Escherichia Coli ◽  
Cell Proliferation ◽  
Protein Synthesis ◽  
Dna Synthesis ◽  
L929 Cell ◽  
Cell Protein ◽  
Fibroblast Proliferation ◽  
Proline Incorporation ◽  
Inhibition Of Dna Synthesis

The effects of Escherichia coli endotoxin upon mouse L929 cell proliferation, DNA synthesis, protein synthesis, and proline incorporation were determined. It was found that a level of endotoxin which inhibited cell proliferation prompted a similar inhibition of DNA synthesis and overall cell protein synthesis. In contrast, endotoxin was shown to inhibit incorporation of proline into cell protein to a significantly greater extent.

ANF-C-receptor-mediated inhibition of aortic smooth muscle cell proliferation and thymidine kinase activity

1994 ◽  
Vol 266 (1) ◽  
pp. R194-R203 ◽  
Author(s):  
P. A. Cahill ◽  
A. Hassid
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Receptor Binding ◽  
Kinase Activity ◽  
Thymidine Kinase Activity ◽  
Aortic Smooth Muscle ◽  
Inhibition Of Dna Synthesis ◽  
Type Receptor

We have investigated the inhibition of DNA synthesis and cell proliferation by rat atrial natriuretic factor [rANF-(99-126)] and several synthetic peptides that bind selectively to the ANF-C-type clearance receptors in subcultured aortic smooth muscle cells. These peptides decreased serum-induced 1) [3H]thymidine incorporation, 2) cell proliferation, and 3) thymidine kinase activity without altering basal or elevated cAMP or cGMP levels. In contrast, another ANF-C-receptor-binding peptide, des[Gln116,Ser117,Gly118,Leu119,Gly120] rANF-(102-121)-NH2 (cANF), failed to decrease serum-induced mitogenesis, yet 100 nM cANF reversed the inhibition of DNA synthesis and cell proliferation and the decrease of thymidine kinase activity elicited by other C receptor-binding peptides, including rANF-(99-126), rANF-(103-125), and porcine C-type natriuretic peptide [pCNP-(1-22)]. Delayed addition experiments indicated that atrial peptides influence a relatively late event (or events) during the G1 phase of the cell cycle. The inhibition of DNA synthesis by C-receptor-binding atrial peptides appeared to be selective for aortic smooth muscle cells, inasmuch as a potent inhibitory agonist peptide, Cys116-rANF-(102-116), was without significant influence on the incorporation of thymidine in cultured rat mesangial cells or bovine pulmonary artery endothelial cells. These results indicate that atrial natriuretic peptide analogues decrease vascular smooth muscle cell mitogenesis and proliferation by a cyclic nucleotide-independent mechanism involving the C-type receptor. Moreover the inhibition of DNA synthesis by rANF-(99-126) and the neuropeptide pCNP-(1-22) appears to be mediated by the ANF-C-type receptor and is associated with inhibition of thymidine kinase activity.

scholarly journals INHIBITION OF DNA SYNTHESIS AND INDUCTION OF LAMBDA PHAGE IN TEMPERATURE SENSITIVE MUTANTS OF ESCHERICHIA COLI

1966 ◽  
Vol 41 (3) ◽  
pp. 247-249 ◽  
Author(s):  
YOSHINOBU SUGINO ◽  
AKIKO SORAI ◽  
TOKIO KOGOMA ◽  
YUKINORI HIROTA ◽  
REIJI OKAZAKI
Keyword(s):  
Escherichia Coli ◽  
Dna Synthesis ◽  
Temperature Sensitive ◽  
Lambda Phage ◽  
Temperature Sensitive Mutants ◽  
Inhibition Of Dna Synthesis

scholarly journals Effect of inhibition of DNA synthesis on u.v. sensitive Bs strains ofEscherichia coli

1969 ◽  
Vol 14 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Michael H. L. Green ◽  
John Donch ◽  
Young S. Chung ◽  
Joseph Greenberg
Keyword(s):  
Escherichia Coli ◽  
Cell Division ◽  
Dna Synthesis ◽  
Nalidixic Acid ◽  
Specific Inhibitor ◽  
Ofescherichia Coli ◽  
Inhibition Of Dna Synthesis ◽  
Division Mechanism

The effect of nalidixic acid, a specific inhibitor of DNA synthesis, onEscherichia colistrain B (lon) and its u.v.-sensitive derivatives is examined. Strain B itself is sensitive to nalidixic acid, whereas its u.v.-resistant derivative B/r is resistant.It is shown that in allexr Astrains, in which u.v.-induced filamentation is suppressed, resistance to nalidixic acid is increased. Amongexr Astrains, Bs4 is exceptionally resistant to nalidixic acid. This is because nalidixic acid kills only growing cells and strain Bs4, atryauxotroph, may grow poorly under the conditions used to test nalidixic acid.Theuvrgenes of the HCR strains Bs1, Bs8 and Bs12 do not suppress u.v.-induced filamentation nor do they affect the response to nalidixic acid. Theuvrgene of strain Bs3 is unusual in increasing the tendency to filament and also sensitivity to nalidixic acid.Strains Bs1, Bs3 and Bs8 are all doubly mutated from strain B, the second mutation (notuvr) being responsible for their increased resistance to nalidixic acid as well as partially or completely suppressing filamentation.It is concluded that the cell division mechanism of (lon) strain B is sensitive to inhibition of DNA synthesis. Mutations which suppress the tendency of strain B to filament reduce its sensitivity to inhibition of DNA synthesis.

scholarly journals Investigations of the Mode of Action and Resistance Development of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections

2013 ◽  
Vol 58 (2) ◽  
pp. 901-908 ◽  
Author(s):  
Hans H. Locher ◽  
Patrick Caspers ◽  
Thierry Bruyère ◽  
Susanne Schroeder ◽  
Philippe Pfaff ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Clostridium Difficile ◽  
Dna Synthesis ◽  
Mode Of Action ◽  
Cross Resistance ◽  
Resistance Development ◽  
Content Type ◽  
Inhibition Of Protein Synthesis ◽  
Inhibitor Of Protein Synthesis ◽  
Inhibition Of Dna Synthesis

ABSTRACTCadazolid is a new oxazolidinone-type antibiotic currently in clinical development for the treatment ofClostridium difficile-associated diarrhea. Here, we report investigations on the mode of action and the propensity for spontaneous resistance development inC. difficilestrains. Macromolecular labeling experiments indicated that cadazolid acts as a potent inhibitor of protein synthesis, while inhibition of DNA synthesis was also observed, albeit only at substantially higher concentrations of the drug. Strong inhibition of protein synthesis was also obtained in strains resistant to linezolid, in agreement with low MICs against such strains. Inhibition of protein synthesis was confirmed in coupled transcription/translation assays using extracts from differentC. difficilestrains, including strains resistant to linezolid, while inhibitory effects in DNA topoisomerase assays were weak or not detectable under the assay conditions. Spontaneous resistance frequencies of cadazolid were low in all strains tested (generally <10−10at 2× to 4× the MIC), and in multiple-passage experiments (up to 13 passages) MICs did not significantly increase. Furthermore, no cross-resistance was observed, as cadazolid retained potent activity against strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new antibiotic fidaxomicin. In conclusion, the data presented here indicate that cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition of DNA synthesis as a potential second mode of action, and suggest a low potential for spontaneous resistance development.

scholarly journals Effect of inhibition of DNA synthesis on mating inEscherichia coliK12

1965 ◽  
Vol 6 (3) ◽  
pp. 479-483 ◽  
Author(s):  
Susan Hollom ◽  
R. H. Pritchard
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Amino Acid Starvation ◽  
The Other ◽  
Thymine Starvation ◽  
Other Hand ◽  
Inhibition Of Dna Synthesis ◽  
Polynucleotide Chain

From studies involving inhibition of DNA synthesis in Hfr strains ofEscherichia coliK12, either by thymine starvation (Pritchard, 1963) or amino-acid starvation (Suit, Matney, Doudney & Billen, 1964), during mating withF−strains, it has been concluded that transfer of DNA from males to females can occur in the absence of DNA synthesis. This conclusion is at variance with the hypothesis (Jacob, Brenner & Cuzin, 1963) that the energy required for transfer is derived from the process of DNA replication. On the other hand, a second prediction from this hypothesis, that one polynucleotide chain of the DNA transferred during mating will have been synthesized during transfer, is strongly supported by recent experiments (Ptashne, 1965; Blinkova, Bresler & Lanzov, 1965; Gross & Caro, 1965).

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