Reciprocal alterations of GMP reductase and IMP dehydrogenase activities during differentiation in HL-60 leukemia cells.
The study was undertaken to elucidate the regulatory roles of GMP reductase (GMPR) and IMP dehydrogenase (IMPDH) on purine interconversion during differentiation. Treatment of HL-60 cells with retinoic acid (1 microM) induced granulocytic differentiation which was accompanied with a 2.4-fold increase in GMPR and 55% decrease in IMPDH activities. Maturation induced by 12-O-tetradecanoylphorbol 13-acetate or dimethylsulfoxide was also associated with similar reciprocal alterations. Incubation with guanosine (200 microM), which expands the guanine nucleotide pool, elevated GMPR (1.9-fold) and decreased IMPDH (73%) activities. The synchronous and opposing alterations in GMPR and IMPDH activities should amplify the metabolic response due to differentiation or guanylate pool expansion.
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
H
H
Nakamura
Y
Y
Natsumeda
M
M
Nagai
J
J
Takahara
S
S
Irino
G
G
Weber
D000227:Adenine Nucleotides / Q000378:metabolism; D002454:Cell Differentiation; D050899:GMP Reductase; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D007168:IMP Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D050899:GMP Reductase