Stimulation of fetal hemoglobin production by short chain fatty acids

Effie Liakopoulou, C. Anthony Blau, Qiliang Li, Betty Josephson, John A. Wolf, Bill Fournarakis, Vidmantas Raisys, George Dover, Thalia Papayannopoulou, George Stamatoyannopoulos

Research output: Contribution to journalArticlepeer-review

Abstract

Butyrate, a four-carbon fatty acid, and its two-carbon metabolic product, acetate, are inducers of γ-globin synthesis. To test whether other short- chain fatty acids share this property, we first examined whether propionic acid, a three-carbon fatty acid that is not catabolized to acetate, induces γ-globin expression. Sodium propionate increased the frequency of fetal hemoglobin containing erythroblasts and the γ/γ + β mRNA ratios in adult erythroid cell cultures and F reticulocyte production in a nonanemic juvenile baboon. Short-chain fatty acids containing five (pentanoic), six (hexanoic), seven (heptanoic), eight (octanoic), and nine (nonanoic) carbons induced γ- globin expression (as measured by increase in γ-positive erythroblasts and γ/γ + β mRNA ratios) in adult erythroid burst-forming unit cultures. There was a clear-cut relationship between the concentration of fatty acids in culture and the degree of induction of γ-globin expression. Three-, four-, and five-carbon fatty acids were better inducers of γ globin in culture as compared with six-to nine-carbon fatty acids. These results suggest that all short-chain fatty acids share the property of γ-globin gene inducibility. The fact that valproic acid, a derivative of pentanoic acid, also induces γ- globin expression suggests that short-chain fatty acid derivatives that are already approved for human use may possess the property of γ-globin inducibility and may be of therapeutic relevance to the β-chain hemoglobinopathies.

Original languageEnglish (US)
Pages (from-to)3227-3235
Number of pages9
JournalBlood
Volume86
Issue number8
DOIs
StatePublished - Oct 15 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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