Superoxide dismutase as an inhibitor of erythroid progenitor cell cycling

Ann N Y Acad Sci. 1991;628:222-32. doi: 10.1111/j.1749-6632.1991.tb17249.x.

Abstract

C57Bl/6 (B6) mice and mice of a congeneic strain, B6S, differ in the proportions of erythroid progenitor cells (BFU-E) typically seen in DNA synthesis in in vivo cell suicide assays, and bone marrow supernatants (MS) prepared from B6 mice can inhibit BFU-E cycling in vitro. Using in vitro BFU-E DNA synthesis assays and a model system of BFU-E in culture (DA-1 cells) as screening methods for the detection of inhibitors of BFU-E cycling, we have purified the protein that is apparently responsible for the inhibitory effects of MS on progenitor cells and that is also an antagonist of the stimulatory effects of interleukin-3 (IL-3) on DA-1 cell proliferation in culture. We have identified this protein as the Cu,Zn-containing form of the antioxidant enzyme superoxide dismutase (SOD), which is normally present in large amounts in erythrocytes. MS from B6S mice does not inhibit BFU-E DNA synthesis. However, measurements of SOD activity showed no differences between B6 and B6S mice; thus the difference between the effects of B6S-MS and B6-MS is not due to differences in the levels of SOD present. The inhibitory effects of SOD on BFU-E in vitro are opposed by the stimulatory effects of IL-3 in a dose-dependent manner, and similar interactions between stimulatory and inhibitory factors also appear to determine the effects of mouse-derived preparations on erythroid cells. If the interactions seen in vitro are applicable to the state in vivo, SOD may be a constitutive inhibitor of erythroid progenitor cell cycling in mice, acting in opposition to stimulatory factors whose expression varies in response to genetic and physiological influences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Erythropoiesis* / drug effects
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Interleukin-3 / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Superoxide Dismutase / pharmacology
  • Superoxide Dismutase / physiology*

Substances

  • Interleukin-3
  • Superoxide Dismutase