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

Abstract

Using antisense technology, the effects of suppressed gene expression of the erythroid-specific delta-aminolevulinate (ALA) synthase (ALAS-E) on heme synthesis, expression of mRNAs encoding an erythroid-specific transcription factor NF-E2, other heme pathway enzymes, and beta-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 beta-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 beta-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 hemin and ALA in the presence of DMSO partially restored the suppressed mRNA levels for beta-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.

• Authors: K Meguro, K Igarashi, M Yamamoto, H Fujita, S Sassa
• Journal: Blood (Blood) Vol. 86 Issue 3 Pg. 940-8 (Aug 01 1995) ISSN: 0006-4971 [Print] United States
• PMID: 7620186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• Erythroid-Specific DNA-Binding Factors
• MafK Transcription Factor
• Mafk protein, mouse
• NF-E2 Transcription Factor
• NF-E2 Transcription Factor, p45 Subunit
• Nfe2 protein, mouse
• RNA, Antisense
• RNA, Messenger
• Transcription Factors
• Heme
• 5-Aminolevulinate Synthetase
• Hydroxymethylbilane Synthase
• Porphobilinogen Synthase

Topics

• 5-Aminolevulinate Synthetase (genetics)
• Animals
• DNA-Binding Proteins (genetics)
• Erythroid Precursor Cells (enzymology)
• Erythroid-Specific DNA-Binding Factors
• Gene Expression Regulation
• Heme (biosynthesis)
• Hydroxymethylbilane Synthase (metabolism)
• In Vitro Techniques
• MafK Transcription Factor
• Mice
• NF-E2 Transcription Factor
• NF-E2 Transcription Factor, p45 Subunit
• Porphobilinogen Synthase (metabolism)
• RNA, Antisense
• RNA, Messenger (genetics)
• Transcription Factors (genetics)
• Tumor Cells, Cultured