Energy and Redox States in the C6 Glioma Cells Following Acute Exposure to Zn, Se+4, and Se+6 and the Correlation with Apoptosis

Abstract

Changes in cellular energy and redox states in the C6 glioma cells exposed to increasing concentrations of either Zn or Se were studied to examine whether different elements cause different patterns of changes in cellular metabolism. Following a 3-h exposure, both Zn and Se+4 caused dose-dependent decreases in cell viability and total adenosine nucleotides (TAN = ATP + ADP + AMP). In addition, Zn caused a dose-dependent increase in cellular ATP/TAN and a decrease in the ADP/TAN and AMP/TAN. These changes resulted in a significant increase in energy charge potential (ECP = [ATP + 0.5ADP]/TAN). Se+4, on the other hand, caused a dose-dependent decrease in ATP/TAN but an increase in both ADP/TAN and AMP/TAN, resulting in a dose-dependent decrease in ECP. Both Zn and Se+4 caused a dose-dependent decrease in GSH/GSSG and an increase in GSH + GSSG when compared to TAN. In contrast to Zn and Se+4, the nontoxic Se+6 caused no significant changes in cellular energy states but reduced the GSH/GSSG ratio from 3.14 ± 0.49 to 2.05 ± 0.29, which could be explained by the effect of Se on enzymes responsible for GSH metabolism. As the cellular ATP level has been considered an important element that mediates the mode of cell death, it was suggested that a significant increase in ATP/TAN upon exposure to Zn would indicate that cell death occurred via apoptosis, while Se+4 caused a different pattern of cell death. This was confirmed by the appearance of cells with fragmented nucleus in cells treated with Zn, but not Se+4 and Se+6. The results demonstrated that different chemicals caused different patterns of metabolic changes. The correlation between metabolic changes and the mode of cell death was discussed.