Butyrate increases the efficiency of translation of γ-globin mRNA

• Published in: Blood Vol. 105; no. 4; pp. 1807 - 1809
• Main Authors: Weinberg, Rona S., Ji, Xinjun, Sutton, Millicent, Perrine, Susan, Galperin, Yelena, Li, Qiliang, Liebhaber, Stephen A., Stamatoyannopoulos, George, Atweh, George F.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.02.2005; The Americain Society of Hematology
• Subjects: Adult; Anemia, Sickle Cell - blood; Arginine - analogs & derivatives; Arginine - pharmacology; Arginine - therapeutic use; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Butyrates - pharmacology; Butyrates - therapeutic use; Fetal Hemoglobin - biosynthesis; Fetal Hemoglobin - genetics; Globins - biosynthesis; Globins - genetics; Globins - metabolism; Humans; Medical sciences; Peptide Chain Initiation, Translational - drug effects; Pharmacology. Drug treatments; Protein Biosynthesis - drug effects; Reticulocytes - drug effects; Reticulocytes - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - blood; Human; Hemoglobinopathy; Sickle cell anemia; Gamma-Peptide chain; Hemopathy; Genetic translation; Genetic disease; Butyrate; Fetal hemoglobin; Globin; Hemolytic anemia; Messenger RNA; Efficiency; Mechanism of action
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-02-0454

Fetal hemoglobin (Hb F) levels increase in most patients with sickle cell disease following intermittent butyrate therapy. Although the full effects of butyrate on Hb F levels usually require multiple treatment cycles, in some patients a peak level is achieved after a few days of butyrate therapy. Our investigation of the mechanism(s) responsible for this rapid induction of Hb F by butyrate showed that reticulocyte γ-globin chain synthesis markedly increased within 24 hours of butyrate exposure, without concomitant changes in reticulocyte γ-globin mRNA levels. This suggests that butyrate might induce Hb F by increasing the efficiency of translation of γ-globin mRNA. This hypothesis was confirmed by ribosome loading studies that demonstrated enrichment of the polysomal fraction of reticulocytes with γ-globin mRNA following butyrate exposure. Thus, the induction of Hb F by butyrate may be mediated by translational effects in addition to its well-known effects on transcription of the γ-globin genes. (Blood. 2005;105:1807-1809)