Erythroleukemia differentiation. Distinctive responses of the erythroid-specific and the nonspecific delta-aminolevulinate synthase mRNA.
We have examined the levels of delta-aminolevulinate synthase (ALAS) mRNAs encoding the erythroid-specific (ALAS-E) and the nonspecific (ALAS-N) ALAS isozymes in murine Friend virus-transformed erythroleukemia (MEL) cells. Both ALAS-E and ALAS-N mRNAs were detected in a clone of dimethyl sulfoxide (Me2SO)-sensitive MEL cells, termed DS-19, without cross-hybridization. Untreated DS-19 cells contained approximately 10-fold more ALAS-E mRNA than ALAS-N mRNA. When DS-19 cells were treated with Me2SO or hemin, ALAS-N mRNA declined rapidly, which was followed by a marked increase in ALAS-E mRNA. Similarly, the immunoquantifiable ALAS-N protein decreased, while the ALAS-E protein increased upon Me2SO treatment. A clone of Me2SO-resistant cells, termed DR-1, which fails to undergo erythroid differentiation, was found to lack ALAS-E mRNA, whereas it showed significant induction responses of mRNAs for other heme pathway enzymes by Me2SO treatment. DR-1 cells contained a similar level of an erythroid-specific transcription factor, GATA-1, as did DS-19 cells, and had neither major deletion nor rearrangement of the ALAS-E gene. These findings indicate that the genes encoding the two ALAS isozymes are under separate controls and suggest that ALAS-E mRNA accumulation is responsible for increased heme synthesis in MEL cells undergoing erythroid differentiation.
Fujita
H
H
Rockefeller University Hospital, New York, New York 10021.
Yamamoto
M
M
Yamagami
T
T
Hayashi
N
N
Sassa
S
S
D000624:5-Aminolevulinate Synthetase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D003854:Deoxyribonucleotides; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis; D006427:Hemin / Q000378:metabolism; D006537:Heptanoates / Q000494:pharmacology; D015151:Immunoblotting; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D003854:Deoxyribonucleotides; D006537:Heptanoates; D012333:RNA, Messenger; C020804:succinylacetone; D006427:Hemin; D005914:Globins; D000624:5-Aminolevulinate Synthetase; D004121:Dimethyl Sulfoxide