CALCIUM IONOPHORE-INDUCED TRANSIENT DOWN-REGULATION OF C-MYB MESSENGER-RNA LEVELS IN FRIEND-ERYTHROLEUKEMIA CELLS

The effects of calcium ionophores A23187 and ionomycin on the c-myb an d c-myc mRNA levels have been investigated in the Friend erythroleukem ia cell line F4-6 using Northern blot analysis. Treatment of the cells with 0.5-4 muM A23187 or 1-4 muM ionomycin induced a concentration-de pendent decrease in c-myb mRNA; this decrease was abolished by EGTA. c -myc mRNA levels were only moderately affected. After 12-24 h of calci um ionophore exposure, c-myb mRNA returned to pretreatment levels. No similar decrease in c-myb mRNA was seen with the sodium ionophore mone nsin (up to 16 muM). The dimethyl sulfoxide-induced suppression of c-m yb and also of c-myc mRNA levels was not prevented in Ca2+-free medium and thus appeared Ca2+-independent. A23187 and ionomycin were capable of inducing beta-globin mRNA synthesis in F4-6 cells. Prolonged calci um ionophore exposure, however, strongly reduced cell viability and re sulted only in a slight hemoglobin increase at lower concentrations. T hese results suggest that a rise in [Ca2+]i may be a signal leading to a transient decrease in c-myb mRNA and the initiation of erythroid di fferentiation in Friend cells. The transient suppression of c-myb mRNA levels represents a common feature of the action of dimethyl sulfoxid e and calcium ionophores.