Energetic and morphological plasticity of C6 glioma cells grown on 3-D support; effect of transient glutamine deprivation.
The energetic metabolism of rat C6 glioma cells has been investigated as a function of the proliferative and differentiation states under three-dimensional (3-D) growing conditions on microcarrier beads. First, the transient deprivation of glutamine from the culture medium induced a marked decrease in the growth rate and a differentiation of C6 cells through the oligodendrocytic phenotype. Second, the respiratory capacity of the C6 cells during short-term subcultures with or without glutamine continuously declined as a function of the cell density, in part due to the mitochondrial content decrease. During the transition from the early exponential to the plateau growth phase in glutamine-containing medium, the oxygen consumption rate per single cell decreased concomitantly with a decrease in the glucose consumption and lactate production rates. This phenomenon led to a sixfold decrease in the total ATP production flux, without significantly affecting the cellular ATP/ADP ratio, thus indicating that some ATP-consuming processes were simultaneously suppressed during C6 proliferation. In glutamine-free medium, the cellular ATP/ADP ratio transiently increased due to growth arrest and to a reduced ATP turnover. Moreover, the results indicated that glutamine is not an essential respiratory substrate for rat C6 glioma under short-term glutamine deprivation. Worth noting was the high contribution of the mitochondrial oxidative phosphorylation toward the total ATP synthesis (about 80%), regardless of the proliferation or the differentiation status of the C6 cells.
Martin
M
M
Institut de Biochimie et de Génétique Cellulaires du CNRS, Bordeaux, France.
Beauvoit
B
B
Voisin
P J
PJ
Canioni
P
P
Guérin
B
B
Rigoulet
M
M
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D019069:Cell Respiration; D004734:Energy Metabolism; D005910:Glioma / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006019:Glycolysis; D051381:Rats; D014407:Tumor Cells, Cultured
D005973:Glutamine