A possible relationship between the regulation of uptake of essential nutrients and the regulation of cell division in higher organisms

| March 22, 2015 | 0 Comments

P M BHARGAVA

Published in: In Regulation of Growth and Differentiated Function in Eukaryote Cells (IUB Symposium no.65) (Raven Press, New York, 1975), pp.79-96.

Abstract:

Some questions pertaining to the control of cell division in higher organisms are stated in Fig. 1. One approach to answering these questions would be through construction of viable models that would attempt to explain the phenomena schematically. One such model, presented here, is based primarily on the following observations.

  1. In higher organisms the ability to exist in the resting state1 appears to go hand in hand with (a) the ability to undergo malignant transformation in which the capacity to revert to the resting state appears to be lost (1, 2); and (b) the occurrence of auxotrophy, i.e., an obligatory requirement for a number of carbon-containing nutrients1 (the “essential nutrients”) that cannot be made by the cell or are made in inadequate quantities (from glucose, for example).
  1. The essential nutrients need to be transported from the environment into both resting cells and dividing cells. In the former they appear to be necessary for maintenance, while in the latter they are required for growth.
  1. The rates of uptake of nutrients in dividing cells appear to be about one order of magnitude greater than the corresponding rates in the same cells in a resting state. For example, we have observed that (a) in BHK cells triggered into division from a simulated resting state the average rate of uptake of amino acids at the time of cell division is approximately 10-fold higher than the rate in the “resting” BHK cells (3), as seen in Table 1; (b) the average rate of uptake of amino acids in rapidly growing Zajdela ascitic hepatoma cells is about threefold higher than the rate obtained in normal adult liver tissue in which most of the cells are in the resting state (4), as seen in Table 2; and (c) the average rate of uptake of amino acids in nongrowing, hyperconfluent, density-inhibited chick embryo fibroblasts is about fivefold lower than the rate observed in the actively growing fibroblasts (5), as seen in Table 3.
  1. The increase in the rate of uptake of nutrients is an early (possibly the earliest) event that occurs when resting cells are triggered into the division cycle. This has been shown, for example, in the case of lectin-stimulated lymphocytes (6-12), target cells stimulated by mitogenic hormones (13-19), liver cells triggered by partial hepatectomy (20, 21), and density inhibited cells in tissue culture stimulated to divide by serum (22-26) or proteolytic enzymes (23, 27, 28). In fact, one of the functions of serum in tissue culture appears to be to ensure that the uptake of nutrients is maintained at the high rate required for sustenance of the dividing state; we have shown that the uptake of amino acids virtually ceases 30 to 60 min after depletion of serum from an actively growing culture of chick embryo fibroblasts (5), as noted in Fig. 2.
  1. The primary event when a resting cell is initiated into the division cycle occurs on the cell surface. Thus cells can be triggered into their division cycle by such agents as lectins, insulin, proteolytic enzymes, and growth hormone without their entering the cell (29-31).
  1. Surface changes are obligatory to and precede malignant transformation. For example, in the case of virally transformed cells, Con A agglutination sites and tumor-specific transplantation antigens appear on the cell surface before manifestation of the malignant phenotype (32, 33); and in temperature-sensitive mutants of oncogenic viruses, surface changes which characterize transformed cells occur at the permissive temperature but not at the nonpermissive temperature (26, 34-36).

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A possible relationship between the regulation of uptake of essential nutrients and the regulation of cell division in higher organisms. P M BHARGAVA. In Regulation of Growth and Differentiated Function in Eukaryote Cells (IUB Symposium no.65) (Raven Press, New York, 1975), pp.79-96.

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