scholarly journals The role of adenosine 3′:5′-cyclic monophosphate in the division of WI 38 cells. The cellular response to prostaglandin E1 and the effects of an cyclic adenosine 3′:5′-cyclic monophosphate analogue and prostaglandin E1 on cell division

1974 ◽  
Vol 142 (2) ◽  
pp. 339-344 ◽  
Author(s):  
Mary J. Kurtz ◽  
Peter Polgar ◽  
Linda Taylor ◽  
Alexander M. Rutenburg

Inhibition of growth and DNA synthesis was observed in WI 38 cells incubated with 8-methylthioadenosine 3′:5′-cyclic monophosphate or prostaglandin E1. The effect of both compounds on cell growth was reversible. On removal of these compounds from culture media the cells initiated DNA synthesis and divided. In addition, prostaglandin E1 stimulated cyclic AMP formation in these cells to over 40 times the normal basal value. The increase in cyclic AMP concentration in WI 38 cells after addition of prostaglandin E1 showed a marked variation. Cells that had recently been treated with trypsin and plated at a lower cell density exhibited a smaller response to addition of prostaglandin E1 than cells that had divided and reached confluence.

1975 ◽  
Vol 150 (1) ◽  
pp. 123-128 ◽  
Author(s):  
B Bächi ◽  
H L Kornberg

1. Cultures of Escherichia coli growing on gluconate use both gluconate and glucose when glucose is added. 2. Glycerol-grown cells adapt to gluconate utilization even in media containing glucose as well as gluconate. 3. The rates of gluconate utilization by cells growing on a mixture of glucose and gluconate, and the specific activities of the gluconate uptake system and of gluconate kinase, are greater if adenosine 3′:5′-cyclic monophosphate (cyclic AMP) is present in the medium than in its absence. 4. Growth on media containing gluconate and cyclic AMP is accompanied by the formation of methyl glyoxal and pyruvate, and progressive inhibition of growth. 5. A mutant devoid of adenylate cyclase activity (cya) grew well on glucose in the absence of exogenous cyclic AMP but grew only poorly on gluconate; neither the gluconate uptake system nor gluconate kinase was adequately induced. The addition of cyclic AMP promoted growth on gluconate and facilitated the induction of proteins required for gluconate catabolism. 6. Phage Pl-mediated transduction of cya+ into the cya-mutant also restored the wild-type phenotype in its ability to adapt to gluconate utilization.


1997 ◽  
Vol 17 (11) ◽  
pp. 6717-6726 ◽  
Author(s):  
S Dremier ◽  
V Pohl ◽  
C Poteet-Smith ◽  
P P Roger ◽  
J Corbin ◽  
...  

Thyrotropin (TSH), via a cyclic AMP (cAMP)-dependent pathway, induces cytoplasmic retractions, proliferation, and differentiation expression in dog thyroid cells. The role of cAMP-dependent protein kinase (PKA) in the induction of these events was assessed by microinjection into living cells. Microinjection of the heat-stable inhibitor of PKA (PKI) inhibited the effects of TSH, demonstrating that activation of PKA was required in this process. Overexpression of the catalytic (C) subunit of PKA brought about by microinjection of the expression plasmid pC alpha ev or of purified C subunit itself was sufficient to mimic the cAMP-dependent cytoplasmic changes and thyroperoxidase mRNA expression but not to induce DNA synthesis and thyroglobulin (Tg) expression. The cAMP-dependent morphological effect was not observed when C subunit was coinjected with the regulatory subunit (RI or RII subunit) of PKA. To mimic the cAMP-induced PKA dissociation into free C and R subunits, the C subunit was coinjected with the regulation-deficient truncated RI subunit (RIdelta1-95) or with wild-type RI or native RII subunits, followed by incubation with TSH at a concentration too low to stimulate the cAMP-dependent events by itself. Although the cAMP-dependent morphology changes were still observed, neither DNA synthesis nor Tg expression was stimulated in these cells. Taken together, these data suggest that in addition to PKA activation, another cAMP-dependent mechanism could exist and play an important role in the transduction of the cAMP signal in thyroid cells.


1974 ◽  
Vol 16 (2) ◽  
pp. 301-307
Author(s):  
P. EKER

Cyclic AMP (0.1 to 1 mM) was found to inhibit the growth of human liver cells in monolayer cultures. Significant amounts of degradation products were not detected in the medium indicating that the growth-inhibiting effect was associated with the intact cyclic nucleotide. DNA synthesis in the liver cell cultures, as measured by thymidine incorporation into acid-insoluble material, was markedly inhibited by cyclic AMP. RNA and protein synthesis were not significantly affected. Cyclic AMP induced a considerable increase in the cellular uptake of thymidine and uridine from the medium. When the liver cells were incubated in medium containing radioactive cyclic AMP, no labelled cyclic AMP could be detected in the acid-soluble cell fraction by chromatographic analysis. It is suggested that cyclic AMP does not enter the liver cells, but that its action on growth and DNA synthesis is somehow mediated through an interaction with the cell surface.


1974 ◽  
Vol 60 (1) ◽  
pp. 249-257 ◽  
Author(s):  
Jeffrey E. Froehlich ◽  
Martin Rachmeler

Incorporation of tritiated thymidine into acid-precipitable material was used to measure the rate of DNA synthesis in secondary cultures of human diploid fibroblasts. Confluent cultures of human diploid fibroblasts, which are synchronized in the G1 phase due to contact inhibition, were released from growth inhibition either by the addition of fresh medium to the cultures or by trypsinization and replating at nonconfluent densities. Either treatment resulted in a synchronous wave of DNA synthesis beginning 10–15 h after treatment and peaking at 20–25 h. In confluent cultures stimulated by fresh medium, either the addition of 0.25 mM N6, O2-dibutyryl-adenosine 3',5'-cyclic monophosphate (db-cAMP) to the medium in the interval 4–8 h after stimulation or the replacement of the fresh medium in that same 4 h interval with the depleted medium present on the cells for the 2 day period before stimulation delayed the synchronous onset of DNA synthesis in the cultures by about 4 h. In nonconfluent cultures freshly seeded from trypsinized confluent cultures, this same depleted medium obtained after a 2 day incubation of fresh medium on confluent cultures is shown to support the progress of the cells into S phase; however, the addition of 0.25 mM db-cAMP to the medium 3½ h after replating still partially prevented the initiation of DNA synthesis in the cultures. The results are discussed in terms of the role of serum and cAMP in the control of cell growth in fibroblast cultures.


1983 ◽  
Vol 116 (3) ◽  
pp. 379-384 ◽  
Author(s):  
Enrique Rozengurt ◽  
Mary K. L. Collins ◽  
Margaret Keehan

1986 ◽  
Vol 250 (4) ◽  
pp. C584-C588 ◽  
Author(s):  
N. E. Owen

The effect of prostaglandin E1 (PGE1) on DNA synthesis was determined using cultured vascular smooth muscle cells. It was found that when PGE1 was added to synchronous, quiescent (growth-arrested) cells, it enhanced DNA synthesis. This was in contrast to the effects of PGE1 on asynchronous, cycling (growing) cells. In these cells, when PGE1 was added, it functioned as an antiproliferative agent. In both cases the effects of PGE1 could be mimicked by 6 alpha-carbaprostacyclin (stable prostacyclin analogue) or by 8-bromo adenosine 3',5'-cyclic monophosphate [a permeable adenosine 3',5'-cyclic monophosphate (cAMP) analogue]. In addition PGE1 was shown to cause an elevation in cellular cAMP levels. On the basis of these studies it is hypothesized that the ultimate effect of addition of PGE1 to vascular smooth muscle cells is dependent on the phase of the cell cycle in which it is added.


1972 ◽  
Vol 79 (3) ◽  
pp. 353-362 ◽  
Author(s):  
J. F. Whitfield ◽  
J. P. Macmanus ◽  
B. M. Braceland ◽  
D. J. Gillan

1960 ◽  
Vol XXXIV (III) ◽  
pp. 411-429 ◽  
Author(s):  
Melvin J. Fregly ◽  
Kenneth M. Cook

ABSTRACT The anti-thyroid drugs, thiouracil, propylthiouracil, and methimazole, prevented both development of elevated blood pressure and cardiac hypertrophy usually accompanying kidney encapsulation with latex envelopes. These drugs also reduced elevated blood pressure of rats with hypertension of 13 to 40 weeks' duration prior to drug administration. Addition of desiccated thyroid powder to diet containing an anti-thyroid drug overcame the anti-hypertensive effect of the latter. Withdrawal of thyroid powder only was followed by return of blood pressure to previous low level within 3 weeks. The results suggest that the anti-hypertensive effect of these drugs is related directly to the hypothyroidism produced rather than to extrathyroidal effects of the drugs. Comparison of potencies of the 3 drugs in terms of anti-hypertensive effect, inhibition of growth rate, increase in testicular size, and increase in thyroid size suggests that propylthiouracil and methimazole are equally potent per unit weight of drug. Thiouracil has approximately half the potency of the other two.


2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.


1993 ◽  
Vol 4 (6) ◽  
pp. 204-209 ◽  
Author(s):  
Wolfgang Schmid ◽  
Doris Nitsch ◽  
Michael Boshart ◽  
Günther Schütz

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