Early metabolic effects of platelet-derived growth factor and transforming growth factor-beta in rat liver in vivo.
The short term metabolic effects of the in vivo administration of platelet-derived growth factor have been examined in the liver of the rat. Meal-fed male Wistar rats weighing between 150-180 g received an intraperitoneal injection of platelet-derived growth factor (17 units/100 g weight), transforming growth factor-beta (185 ng/100 g weight), or saline. At 5 min after injection, the livers were freeze-clamped. Samples of the tissue were subsequently assayed for metabolite content and enzyme activities. Platelet-derived growth factor injection caused an elevation in the liver content of pyruvate from 0.14 +/- 0.012 to 0.19 +/- 0.009 mumol/g wet weight liver (p less than or equal to 0.01) and an increase in the cytosolic phosphorylation potential [sigma ATP]/[sigma ADP][sigma Pi] from 6670 +/- 540 to 8970 +/- 750 (p less than or equal to 0.01). In addition an increase in the hepatic content of the hexose monophosphate pathway metabolites, 6-phosphogluconate (0.027 +/- 0.004 to 0.037 +/- 0.005 mumol/g wet weight) (p less than or equal to 0.05), ribulose 5-phosphate (0.013 +/- 0.001 to 0.017 +/- 0.001 mumol/g wet weight) (p less than or equal to 0.05) and combined sedoheptulose 7-phosphate and ribose 5-phosphate (0.052 +/- 0.007 to 0.062 +/- 0.004 mumol/g wet weight) (p less than or equal to 0.05) was observed. The elevation in the hexose monophosphate pathway metabolites resulted from a 1.3-fold elevation in the activity of glucose-6-phosphate dehydrogenase [EC 1.1.1.49] when measured in a crude homogenate. Kinetic analysis performed on partially purified glucose-6-phosphate dehydrogenase demonstrated no significant change in the Km of the enzyme for either NADP+ or glucose 6-phosphate, while a 2.4-fold increase in the Vmax was observed. In view of the rapidity of the change in total measured enzyme activity and increase in the Vmax of glucose-6-phosphate dehydrogenase, it is postulated that platelet-derived growth factor causes a covalent modification of the existing enzyme. Transforming growth factor-beta caused no change in the hepatic metabolite content in the treated animals when compared to saline treated controls.
Reed
B Y
BY
King
M T
MT
Gitomer
W L
WL
Veech
R L
RL
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015291:Transforming Growth Factors
D006131:Growth Inhibitors; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D009243:NAD; D009249:NADP; D000244:Adenosine Diphosphate; D015291:Transforming Growth Factors; D000255:Adenosine Triphosphate; D005954:Glucosephosphate Dehydrogenase