Inhibition of spermidine and spermine synthesis leads to growth arrest of rat embryo fibroblasts in G1
- 4 February 1978
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 94 (2), 161-170
- https://doi.org/10.1002/jcp.1040940205
Abstract
Following growth stimulation of rat embryo fibroblast (REF) cells previously arrested in G1 by serum deprivation, there occurs a large increase in the synthesis of the polyamines putrescine, spermidine and spermine. Methylglyoxal bis(guanylhydrazone) (MGBG), a potent inhibitor of S‐adenosylmethionine decarboxylase can block the accumulation of both spermidine and spermine over a period of several days. Under such conditions REF cells treated with MGBG will approximately double in number and then become growth‐arrested again predominantly in the G1 phase of the cell cycle. REF cells therefore appear to contain sufficient spermidine and spermine to progress through one cell cycle before the intracellular levels of these polyamines is reduced sufficiently to arrest growth in the absence of continued polyamine synthesis. Limitation of intracellular polyamine levels is therefore not the mechanism by which deprivation of serum growth factors arrests cell growth. While continued growth is nevertheless dependent on polyamine synthesis, this cell type is capable of limited proliferation in its absence. Addition of spermidine or spermine to MGBG‐arrested REF cells results in a rapid resumption of proliferation demonstrating that either polyamine can fulfill the role played by these polyamines in the growth process. Low levels of spermidine and spermine therefore arrest this cell type at a resriction point in G1 at which it is decided whether the intracellular level of these polyamines is sufficiently high to enable a cell to enter into and complete a new cell cycle. This polyamine‐sensitive restriction point is considered to be analogous to the restriction point(s) in G1 at which serum and nutrient limitation act.This publication has 36 references indexed in Scilit:
- A possible involvement of polyamines in the initiation of DNA synthesis by human WI-38 and mouse BALB/3T3 cellsJournal of Cellular Physiology, 1976
- Growth Regulation in Cultures of Embryonic Rat Fibroblasts by the Serum Factors S1 and S2Published by Elsevier ,1975
- Fibroblastoid and epithelioid cells in tissue culture: Differences in sensitivity to ouabain and to phospholipid compositionBiochimica et Biophysica Acta (BBA) - General Subjects, 1974
- Specific induction of ornithine decarboxylase in 3T3 mouse fibroblasts by pituitary growth factors. Cell density-dependent biphasic response and alteration of half-lifeBiochemistry, 1974
- Initiation of DNA Synthesis in Primary Fetal Rat Hepatocytes in CultureExperimental Biology and Medicine, 1974
- Effect of methylglyoxal bis(guanylhydrazone) on polyamine metabolism in normal and regenerating rat liver and rat thymusBiochemical Journal, 1973
- Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone)Biochemical Journal, 1973
- Stimulation by estrogens of ornithine and S-adenosylmethionine decarboxylases in the immature rat uterusBiochimica et Biophysica Acta (BBA) - General Subjects, 1971
- Cytotoxic effect of oxidized spermine on Ehrlich ascites cellsBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1967
- Complex formation with DNA and inhibition of nucleic acid synthesis by methylglyoxal bis(guanylhydrazone)Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1965