Calcium ionophore-induced transient down-regulation of c-myb mRNA levels in Friend erythroleukemia cells.
The effects of calcium ionophores A23187 and ionomycin on the c-myb and c-myc mRNA levels have been investigated in the Friend erythroleukemia cell line F4-6 using Northern blot analysis. Treatment of the cells with 0.5-4 microM A23187 or 1-4 microM ionomycin induced a concentration-dependent decrease in c-myb mRNA; this decrease was abolished by EGTA. c-myc mRNA levels were only moderately affected. After 12-24 h of calcium ionophore exposure, c-myb mRNA returned to pretreatment levels. No similar decrease in c-myb mRNA was seen with the sodium ionophore monensin (up to 16 microM). The dimethyl sulfoxide-induced suppression of c-myb and also of c-myc mRNA levels was not prevented in Ca(2+)-free medium and thus appeared Ca(2+)-independent. A23187 and ionomycin were capable of inducing beta-globin mRNA synthesis in F4-6 cells. Prolonged calcium ionophore exposure, however, strongly reduced cell viability and resulted only in a slight hemoglobin increase at lower concentrations. These 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 differentiation in Friend cells. The transient suppression of c-myb mRNA levels represents a common feature of the action of dimethyl sulfoxide and calcium ionophores.
Department of Toxicology, Hamburg University Medical School, Federal Republic of Germany.
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Schaefer
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Stöcker
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Marquardt
D000199:Actins / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology*; D005622:Friend murine leukemia virus; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009857:Oncogenes / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000199:Actins; D006454:Hemoglobins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D000001:Calcimycin; D004533:Egtazic Acid; D015759:Ionomycin; D004121:Dimethyl Sulfoxide