Histochemical evaluation of energy metabolism in rat glioma.
The key enzymes of oxidative phosphorylation and glycolysis were evaluated histochemically in rat-implanted C6 gliomas using spot densitometry. Hexokinase, the initial enzyme for the glycolysis pathway, was 40% higher within tumour than the contralateral cerebral cortex. A similar increase within tumours for 2-deoxyglucose was observed by autoradiography. Glucose-6-phosphate dehydrogenase (G6PDH), which is the first enzyme in the pentose phosphate pathway, shunting glucose towards nucleic acid synthesis, was more than 300% higher in gliomas compared with the normal cortex. In contrast, enzymes in the energy producing tricarboxylic acid cycle (succinate-, isocitrate-, and malate-dehydrogenase) and in the electron-transport system (cytochrome c oxidase) were significantly reduced in tumour (58% less than the contralateral cortex). Lactate dehydrogenase activity, which converts pyruvate to lactate, was 50% higher within tumour. Significant reductions of enzymatic activities also occurred in non-neoplastic tissue in ipsilateral hemisphere, with larger tumours. Some enzymes showed heterogeneous activity within tumours, especially G6PDH. These results suggest that: (1) energy production is more dependent on lactate production than on oxidative phosphorylation in C6 glioma, and (2) a significant part of the increased glucose utilization in glioma cells is due to increased activity of the pentose phosphate shunt for increased DNA synthesis, and not energy production.
Ikezaki
K
K
Division of Neurosurgery, Jonsson Cancer Center, University of California Los Angeles School of Medicine 90024.
Black
K L
KL
Conklin
S G
SG
Becker
D P
DP
D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism; D004798:Enzymes / Q000032:analysis; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006019:Glycolysis; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D010085:Oxidative Phosphorylation; D051381:Rats; D014407:Tumor Cells, Cultured
D004798:Enzymes; D009363:Neoplasm Proteins