Inhibition of hemopoietic growth factor-induced proliferation by adenosine diphosphate-ribosylation inhibitors

G. Colon-Otero, J. J. Sando, J. L. Sims, E. McGrath, D. E. Jensen, P. J. Quesenberry

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The effects of adenosine diphosphate (ADP) ribosylation inhibitors on hematopoietic growth factor-induced proliferation were examined. Significant inhibition of interleukin-3 (IL-3), colony-stimulating factor 1, and lung conditioned media-induced clonal agar growth of normal murine hematopoietic cells by 10 mmol/L nicotinamide (NAM), 10 mmol/L 3-aminobenzamide (3AB), and 5 mmol/L N1-methylnicotinamide (1MN) was noted. Nicotinic acid, a related compound that does not inhibit ADP ribosylation, failed to inhibit the growth factor-mediated proliferation. NAM (10 mmol/L), 3AB (10 mmol/L), and 1MN (5 mmol/L) also prevented IL-3 and phorbol ester-stimulated 3H-thymidine incorporation into the IL-3-responsive FDC-P1 cell line. Exposure of FDC-P1 cells to 10 mmol/L NAM led to a significant decrease in nuclear poly-(ADP-ribose) levels. Exposure of FDC-P1 cells to 5 mmol/L 1 MN did not affect the interaction of the phorbol ester, protein kinase-C (PK-C), with the cell membrane as determined by assay of phorbol ester binding in cytosol and membrane preparations. Nor did it affect the catalytic activity of PK-C as determined by assaying the in vitro phosphorylation of histone H1 by cytosolic kinase preparations from FDC-P1 as well as EL4 thymoma cells. 1MN markedly enhanced the inhibitory effects of phorbol esters on DNA synthesis of EL4 cells even at concentrations (1.25 mmol/L) that had no effects on DNA synthesis in the absence of phorbol esters. Our findings demonstrate that (a) active ADP ribosylation inhihibitors interfere with growth factor-induced proliferation of murine hematopoietic cells and (b) the inhibition occurs at a step that follows the activation and translocation of PK-C and is more closely linked to DNA synthesis.

Original languageEnglish (US)
Pages (from-to)686-693
Number of pages8
JournalBlood
Volume70
Issue number3
StatePublished - Dec 1 1987

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Colon-Otero, G., Sando, J. J., Sims, J. L., McGrath, E., Jensen, D. E., & Quesenberry, P. J. (1987). Inhibition of hemopoietic growth factor-induced proliferation by adenosine diphosphate-ribosylation inhibitors. Blood, 70(3), 686-693.