5-Aminolevulinate synthase expression and hemoglobin synthesis in a human myelogenous leukemia cell line.
We examined the effect of hemin, TGF-beta1 and cytosine arabinoside (Ara-C) on the levels of mRNAs for the erythroid-specific 5-aminolevulinate synthase (ALAS-E) and gamma-globin in various human myelogenous leukemia cell lines. Detailed analyses were also made using one of them, YN-1, which was isolated and established in culture from a patient with chronic myelogenous leukemia. Our results demonstrate that gamma-globin protein level and the percentage of benzidine-positive cells in the cell line increased markedly (10- to 30-fold) upon treatment with hemin, TGF-beta1, or Ara-C. In contrast, gamma-globin mRNA was already markedly expressed prior to treatment in 4 out of 9 cell lines examined, including YN-1, and the level increased only marginally after treatment with hemin. ALAS-E mRNA levels were increased in YN-1 cells after treatment with TGF-beta1 and Ara-C, while hemin treatment had little effect. These results indicate that heme supply is insufficient in YN-1 cells and suggest that hemin increases hemoglobin synthesis principally at the post-transcriptional level, whereas TGF-beta1 and Ara-C stimulate hemoglobin synthesis by activating efficient endogenous heme supply in the cells.
Nagai
T
T
Department of Biochemistry, Tohoku University School of Medicine, Sendai.
Harigae
H
H
Furuyama
K
K
Munakata
H
H
Hayashi
N
N
Endo
K
K
Sassa
S
S
Yamamoto
M
M
D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics
D006454:Hemoglobins; D012333:RNA, Messenger; D003561:Cytarabine; D005346:Fibroblast Growth Factors; D006427:Hemin; D000624:5-Aminolevulinate Synthetase