A1 Refereed original research article in a scientific journal
Adenosine inhibits DNA synthesis stimulated with TSH, insulin, and phorbol 12-myristate 13-acetate in rat thyroid FRTL-5 cells
Authors: Vainio M, Saarinen P, Tornquist K
Publisher: WILEY-LISS
Publication year: 1997
Journal:: Journal of Cellular Physiology
Journal name in source: JOURNAL OF CELLULAR PHYSIOLOGY
Journal acronym: J CELL PHYSIOL
Volume: 171
Issue: 3
First page : 336
Last page: 342
Number of pages: 7
ISSN: 0021-9541
DOI: https://doi.org/10.1002/(SICI)1097-4652(199706)171:3336::AID-JCP12>3.0.CO;2-8
Abstract
Adenosine has been shown to modulate cell proliferation in FRTL-5 thyroid cells, although the mechanisms by which this interaction occurs is still unclear. In the present study we investigated the effects of adenosine on the H-3-thymidine incorporation, cell cycle kinetics, and expression of the transcription factor c-Fos in cells stimulated via three different mitogenic pathways, i.e., by thyroid stimulating hormone (TSH) [adenosine 3',5'-cyclic monophosphate(cAMP)], insulin (tyrosine kinase), or phorbol 12-myristate 13-acetate (protein kinase C). Addition of adenosine to cells grown in medium containing hormones and serum did not inhibit the incorporation of H-3-thymidine. If adenosine was added to hormone-deprived cells together with any of the tested mitogens, the stimulation of the H-3-thymidine incorporation was inhibited in a dose-dependent manner. The inhibition was significantly lower when the cells were preincubated with TSH or insulin for 48 h. Flow cytometric studies showed that adenosine evoked an inhibition of the cells in the G(0)/G(1) phase. Submaximal doses of adenosine (10 nM-10 mu M) were able to induce c-Fos expression in FRTL-5 cells. However, the mitogen-induced expression of c-Fos was not reduced by maximal dose of adenosine (100 mu M). The effect of adenosine on DNA synthesis was not dependent on pertussis toxin-sensitive C-proteins. In addition, adenosine A(1)- or A(2)-receptor antagonists did not block the effect of adenosine. The effect of adenosine was abolished by treatment of the cells with adenosine deaminase, suggesting that the observed effect was not mediated by a metabolite of adenosine. The results suggest that adenosine is an effective blocker of mitogen-evoked DNA synthesis of FRTL-5 cells, provided that adenosine is administered simultaneously with the mitogen. (C) 1997 Wiley-Liss, Inc.
Adenosine has been shown to modulate cell proliferation in FRTL-5 thyroid cells, although the mechanisms by which this interaction occurs is still unclear. In the present study we investigated the effects of adenosine on the H-3-thymidine incorporation, cell cycle kinetics, and expression of the transcription factor c-Fos in cells stimulated via three different mitogenic pathways, i.e., by thyroid stimulating hormone (TSH) [adenosine 3',5'-cyclic monophosphate(cAMP)], insulin (tyrosine kinase), or phorbol 12-myristate 13-acetate (protein kinase C). Addition of adenosine to cells grown in medium containing hormones and serum did not inhibit the incorporation of H-3-thymidine. If adenosine was added to hormone-deprived cells together with any of the tested mitogens, the stimulation of the H-3-thymidine incorporation was inhibited in a dose-dependent manner. The inhibition was significantly lower when the cells were preincubated with TSH or insulin for 48 h. Flow cytometric studies showed that adenosine evoked an inhibition of the cells in the G(0)/G(1) phase. Submaximal doses of adenosine (10 nM-10 mu M) were able to induce c-Fos expression in FRTL-5 cells. However, the mitogen-induced expression of c-Fos was not reduced by maximal dose of adenosine (100 mu M). The effect of adenosine on DNA synthesis was not dependent on pertussis toxin-sensitive C-proteins. In addition, adenosine A(1)- or A(2)-receptor antagonists did not block the effect of adenosine. The effect of adenosine was abolished by treatment of the cells with adenosine deaminase, suggesting that the observed effect was not mediated by a metabolite of adenosine. The results suggest that adenosine is an effective blocker of mitogen-evoked DNA synthesis of FRTL-5 cells, provided that adenosine is administered simultaneously with the mitogen. (C) 1997 Wiley-Liss, Inc.
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