Metabolic adaptation during erythropoietin-mediated terminal
differentiation of mouse erythroid cells
HD Kim, MJ Koury, SJ Lee, JH Im and ST Sawyer
Department of Pharmacology, University of Missouri-Columbia 65212.
Metabolic development was examined in erythroid precursor cells, which were
isolated from the spleens of mice infected with the anemia- inducing strain
of Friend virus (FVA cells). FVA cells undergo differentiation in vitro
from the proerythroblast stage through the reticulocyte stage over a
48-hour period in the presence of erythropoietin. Concomitant with marked
decreases in cellular size and energy demand, metabolic capacities of both
glycolysis and oxygen consumption diminish after 48 hours in culture by 7-
and 18-fold, respectively. Because the oxidative capacity decreases more
than glycolytic ability does, the metabolic machinery increasingly shifts
toward anaerobic metabolism. During the 48-hour period of differentiation,
the 2,3-diphosphoglyceric acid (DPG) content per cell and 2,3-DPG mutase
activity per cell increased eightfold and threefold, respectively. Freshly
harvested FVA cells have adenosine triphosphate (ATP) levels of 7.23 +/-
2.52 mumol/10(10) cells or 3.76 +/- 1.31 mumol/mL cell water which are 12-
or 2.3-fold higher, respectively, than the ATP levels of mature red blood
cells. In the course of FVA cell differentiation, ATP content per cell
decreases by fourfold, but ATP concentration in cell water remains
unchanged because of a corresponding decrease in cellular size and water
content during differentiation. These studies show that in the face of
dramatic decreases in cell size and cellular energy demand, terminally
differentiating erythroid cells maintain a constant ATP level by undergoing
an involution of their glycolytic machinery as well as by losing their
aerobic metabolic capacity.
Volume 77,
Issue 2,
pp. 387-392,
01/15/1991
Copyright © 1991 by The American Society of Hematology
