Inhibition of hemoglobin synthesis by cyanate in vitro

B. P. Alter, Y. W. Kan, D. G. Nathan

Research output: Contribution to journalArticle

Abstract

Cyanate inhibits sickling and prolongs red cell survival in sickle cell anemia. However, cyanate markedly inhibits hemoglobin synthesis in vitro. Incorporation of radioactive amino acid into hemoglobin by human sickle reticulocytes or bone marrow and by rabbit reticulocytes (whole cell or cell free lysate) was inhibited by as little as 2 mM cyanate and abolished by 50 mM. Both alpha and beta S chains were equally affected. The inhibition was only partially reversible by washing the cells after exposure to cyanate. Transport of radioactive amino acid into the cell was not impaired, and free intracellular amino acid was not carbamylated. Aminoacylation of transfer RNA was not inhibited; the acylated amino acid was not carbamylated. Examination of polysome patterns by sucrose density gradient centrifugation revealed degradation of polysomes to monosomes, suggesting inhibition of initiation of protein synthesis by cyanate. In a cell free lysate, cyanate prevented hemin stimulation of initiation. It is concluded that cyanate profoundly inhibits initiation of hemoglobin synthesis in vitro.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalBlood
Volume43
Issue number1
StatePublished - 1974
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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    Alter, B. P., Kan, Y. W., & Nathan, D. G. (1974). Inhibition of hemoglobin synthesis by cyanate in vitro. Blood, 43(1), 57-68.