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The role of the erythroid-specific delta-aminolevulinate synthase gene
expression in erythroid heme synthesis
K Meguro, K Igarashi, M Yamamoto, H Fujita and S Sassa
Rockefeller University, New York, NY 10021, USA.
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.
Volume 86,
Issue 3,
pp. 940-948,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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