Activin A/erythroid differentiation factor induces thromboxane A2 synthetic activity in murine erythroleukemia cells.
Activin A, a protein homologous to transforming growth factor beta, was shown to induce hemoglobin synthesis in murine erythroleukemia (MEL) cells and was also termed erythroid differentiation factor (EDF) (Eto, Y., Tsuji, T., Takezawa, M., Takano, S., Yokogawa, Y., and Shibai, H. (1987) Biochem. Biophys. Res. Commun. 142, 1095-1103). We found that activin A/EDF also induced thromboxane (TX) A2 synthetic activity in these cells. Synthesis of TXA2 from arachidonic acid is catalyzed by cyclooxygenase and TX synthase. Activin A/EDF induced the latter TX synthase activity, whereas the cyclooxygenase activity was constitutively expressed. The induction of this enzyme activity was inhibited by cycloheximide, suggesting that activin A/EDF induced de novo protein synthesis of TX synthase. Furthermore, we studied the relationship between the induction of TXA2 synthetic activity and erythroid differentiation in MEL cells, since the former is not an erythroid phenotype. We found 1) that the two responses to activin A/EDF were distinctly affected by the initial cell density; 2) that the dose-response curves for activin A/EDF were similar (ED50 = approximately 100 pM), whereas the time course of induction of TXA2 synthetic activity was much faster; and 3) that other erythroid differentiation inducers of MEL cells, namely dimethyl sulfoxide and hexamethylene bisacetamide, had little or no effect on TXA2 synthesis. These results indicate that activin A/EDF induces TXA2 synthetic activity independently of erythroid differentiation.
Yamashita
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T
Fourth Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Shimizu
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Ogata
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D000110:Acetylcholinesterase / Q000378:metabolism; D028341:Activins; D000818:Animals; D001345:Autoradiography; D002454:Cell Differentiation / Q000187:drug effects; D002855:Chromatography, Thin Layer; D003513:Cycloheximide / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D013928:Thromboxane A2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006454:Hemoglobins; D028341:Activins; D007265:Inhibins; D013928:Thromboxane A2; D003513:Cycloheximide; D000110:Acetylcholinesterase; D013930:Thromboxane-A Synthase