Importance of glucose-6-phosphate dehydrogenase activity for cell growth.
The intracellular redox potential, which is determined by the level of oxidants and reductants, has been shown to play an important role in the regulation of cell growth. The principal intracellular reductant is NADPH, which is mainly produced by the pentose phosphate pathway through the actions of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and by 6-phosphogluconate dehydrogenase. Previous research has suggested that an increase in G6PD activity is important for cell growth. In this article, we suggest that G6PD activity plays a critical role in cell growth by providing NADPH for redox regulation. The results show the following: 1) inhibition of G6PD activity abrogated growth factor stimulation of [3H]thymidine incorporation in all cell lines tested; 2) overexpression of G6PD stimulated cell growth, as measured by an increase in [3H]thymidine incorporations as compared with cells transfected with vector alone; 3) inhibition of G6PD caused cells to be more susceptible to the growth inhibitory effects of H2O2; 4) inhibition of G6PD led to a 30-40% decrease in the NADPH/NADP ratio; and 5) inhibition of G6PD inhibited cell anchorage and significantly decreased the growth-related stimulation of tyrosine phosphorylation.
Tian
W N
WN
Renal Division and Department of Medicine, Beth Israel Deaconess Medical Center, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Braunstein
L D
LD
Pang
J
J
Stuhlmeier
K M
KM
Xi
Q C
QC
Tian
X
X
Stanton
R C
RC
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002455:Cell Division; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D012267:Ribosemonophosphates / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D004791:Enzyme Inhibitors; D012267:Ribosemonophosphates; D014443:Tyrosine; D003687:Dehydroepiandrosterone; C031626:ribose-5-phosphate; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D013936:Thymidine