AJP - Cell Physiology, Vol 253, Issue 6 C797-C801, Copyright © 1987 by American Physiological Society
Effects of low calcium levels on erythropoietin production by human renal carcinoma cells in culture
K. Nagakura, M. Ueno, J. Brookins, B. S. Beckman and J. W. Fisher
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Recent investigations have shown that calcium entry blockers enhance the
effects of hypoxia on erythropoietin (Ep) production in vivo. To determine
whether deprivation of calcium increases Ep production and/or release,
studies were carried out to determine the effects of low levels of
extracellular calcium on Ep (radioimmunoassay) secretion in human renal
carcinoma cells in culture. Low extracellular calcium levels (0.3 mM) in
culture medium significantly (P less than 0.01) enhanced Ep secretion
(64-145% increase per day) by renal carcinoma cells in culture when
compared with a concentration of 1.9 mM calcium in the control culture
medium (23-68% increase per day) incubated for 24 h or more. A 53% increase
per day in Ep secretion was also produced by the calmodulin inhibitor
trifluoperazine. To determine whether the effects of low calcium levels on
Ep production could be due to nonspecific leakage of large intracellular
molecules caused by a permeabilization of the cell membrane, the effect of
low calcium levels in the cultures of the renal carcinoma cells on lactate
dehydrogenase release into the culture medium was studied. Low calcium
concentrations failed to significantly enhance lactate dehydrogenase
secretion by the renal carcinoma cells. In conclusion, our results indicate
a possible involvement of the calcium ion and calmodulin in the
biosynthetic pathway for Ep and that calcium may exert a suppressive effect
on Ep production.
