Glucocorticoids inhibit the coordinated translation of alpha- and beta-globin mRNAs in Friend erythroleukemia cells.
The dimethylsulfoxide (Me2SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10(-5) to 10(-8) M inhibits by 90-30% and fluocinolone acetonide at concentrations of 10(-8) to 10(-11) M shows a greater than 90% inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the alpha- and beta-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and that the expression of some of these, in addition to alpha- and beta-globin, is affected by glucocorticoids. The levels of alpha- and beta-globin mRNAs are very close to fully induced levels and preclude transcription as a major site for glucocorticoid control. In addition, it has been shown that glucocorticoids inhibit the translation of alpha- and beta-globin mRNAs, that the level of this inhibition is concentration dependent, and that the translation of beta-globin mRNA is slightly more sensitive to inhibition than the translation of alpha-globin mRNA. It is concluded that, although the translation of alpha- and beta-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of alpha- and beta-globin synthesized. Thus, part of this mechanism may involve a differential sensitivity of alpha- and beta-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.
D000818:Animals; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005914:Globins / Q000235:genetics*; D005938:Glucocorticoids / Q000494:pharmacology*; D006454:Hemoglobins / Q000096:biosynthesis*; D007525:Isoelectric Focusing; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*
D005938:Glucocorticoids; D006454:Hemoglobins; D012333:RNA, Messenger; D005914:Globins; D004121:Dimethyl Sulfoxide