Partial prevention of compactin (ML-236B) inhibition of in vitro hematopoiesis by dolichol and dolichyl phosphate.
We have reported that the exogenous addition of dolichyl phosphate (Dol-P) enhances the colony-forming capacities of early erythroid progenitors (BFU-E), late erythroid progenitors (CFU-E), and granulocyte-macrophage progenitors (CFU-GM) in adult mouse bone marrow, and that dolichol (Dol) enhances that of only CFU-E (Int. J. Cell Cloning 3:313, 1985). Compactin (2.5-10 microM), a specific inhibitor of mevalonate biosynthesis that causes a decrease of endogenous Dol biosynthesis, inhibited colony formation of CFU-GM. Exogenous addition of Dol-P partially prevented this inhibition, but Dol and the other mevalonate metabolites, such as cholesterol, coenzyme Q10, and isopentenyladenine, could not. In addition, we have found that the colony-forming capacity of CFU-E in fetal mouse liver was not enhanced by exogenous Dol or Dol-P. But the decrease of colony formation or DNA synthesis of fetal CFU-E in the presence of compactin was prevented by the exogenous addition of Dol or Dol-P.
D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D004288:Dolichol Phosphates / Q000494:pharmacology; D004286:Dolichols / Q000494:pharmacology*; D004920:Erythropoiesis / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000196:embryology; D008148:Lovastatin / Q000031:analogs & derivatives*; D008264:Macrophages / Q000166:cytology; D008798:Mevalonic Acid / Q000502:physiology; D051379:Mice; D009281:Naphthalenes / Q000037:antagonists & inhibitors*
D004224:Diterpenes; D004288:Dolichol Phosphates; D004286:Dolichols; D009281:Naphthalenes; C012258:mevastatin; D008148:Lovastatin; D008798:Mevalonic Acid