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.
Nakamura
H
H
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
Natsumeda
Y
Y
Nagai
M
M
Takahara
J
J
Irino
S
S
Weber
G
G
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