Figure 8

Possible role of AICAR and compound C on the AMPK pathway and on glycolysis in CT-2A and astrocytes under low glucose conditions. AICAR stimulates AMPK phosphorylation and glycolysis by increasing glucose uptake in the cells. Under low glucose conditions, increased AMP/ATP ratio stimulates AMPK and glycolysis both in astrocytes and CT-2A. The presence of an intact TSC2- mTOR signaling pathway in astrocytes helps to reduce protein sysnthesis to conserve energy and thus prevents apoptosis. Sustained mTOR-S6 kinase pathway activity enhances apoptosis in TSC2 deficient CT-2A cells under low glucose conditions. compound C, on the other hand, inhibits AMPK phosphorylation and glycolysis in the cells. Thus, although normal astrocytes downregulate protein synthesis under low glucose conditions as an adaptation to conserve energy for survival, the decrease in glycolytic ATP production due to compound C results in increased apoptosis.