The role of the erythroid-specific δ-aminolevulinate synthase gene expression in erythroid heme synthesis

Kuniaki Meguro, Kazuhiko Igarashi, Masayuki Yamamoto, Hiroyoshi Fujita, Shigeru Sassa

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Using antisense technology, the effects of suppressed gene expression of the erythroid-specific δ-aminolevulinate (ALA) synthase (ALAS-E) on heme synthesis, expression of mRNAs encoding an erythroid-specific transcription factor NF-E2, other heme pathway enzymes, and β-globin were examined in murine erythroleukemia (MEL) cells. In MEL cells in which an antisense ALAS- E RNA was expressed (AS clone), sense ALAS-E mRNA levels in both untreated and dimethylsulfoxide (DMSO)-treated cells were decreased compared with their respective controls. Heme synthesis in AS clones was decreased in proportion to the suppressed levels of ALAS-E mRNA. In addition, mRNAs for ALA dehydratase, porphobilinogen deaminase, ferrochelatase (FeC), and β-globin were also decreased in AS clones. There was a strong correlation between the level of ALAS-E mRNA and most of the mRNAs of the heme pathway enzymes and β-globin. There was a decrease in the mRNA level of p45, but not of mafK, which are the large and the small subunits of NF-E2, respectively, in AS clones. Treatment of AS cells with heroin and ALA in the presence of DMSO partially restored the suppressed mRNA levels for β-globin and FeC and heme content, respectively. These findings thus indicate that heme formation, which is determined by the level of ALAS-E, plays an essential role on gene expression of many proteins necessary for erythroid development.

Original languageEnglish
Pages (from-to)940-948
Number of pages9
JournalBlood
Volume86
Issue number3
DOIs
Publication statusPublished - 1995 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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