Metabolic effects of galactose on human HepG2 hepatoblastoma cells.
HepG2 cells were used as a model system to study the effects of galactose overload on the liver, a target organ of galactose toxicity in patients suffering from transferase-deficient galactosemia. In the presence of galactose, HepG2 cell growth was slow and the pattern of gene expression remained characteristic of liver cells (secretion of alpha-fetoprotein [AFP] albumin, and transferrin). Galactose-1-phosphate (Gal-1-P) accumulated, as it does in galactosemic cells, but did not affect the energetic status of the cells (no adenosine triphosphate [ATP] depletion). However, the substitution of galactose for glucose as the sole hexose in the medium affected the specific activities of the galactose-metabolizing enzymes. Galactokinase (GALK) activity was decreased, and those of galactose-1-phosphate uridyltransferase (GALT), phosphoglucomutase, and glucose-6-phosphate dehydrogenase (G6PDH) were increased. The conversion of radiolabeled galactose to glucose (CO2 production and glycogen level) was greater in galactose medium than in glucose medium after a 7-day culture. Therefore, the culture of HepG2 cells in galactose medium indicates that the enhanced utilization of this hexose is due to the increased enzyme activities regulating its own metabolism. Hence, HepG2 cells constitute a good model for the study of modulation of galactose-metabolizing enzymes by galactose.
Davit-Spraul
A
A
Laboratoire de Biochimie Appliquée, Faculté de Pharmacie-Paris-XI, Chatenay-Malabry, France.
Pourci
M L
ML
Soni
T
T
Lemonnier
A
A
D000704:Analysis of Variance; D001798:Blood Proteins / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D016923:Cell Death; D005690:Galactose / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D018197:Hepatoblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010733:Phosphoglucomutase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D002245:Carbon Dioxide; D005954:Glucosephosphate Dehydrogenase; D010733:Phosphoglucomutase; D005690:Galactose