Apoptosis induced by growth factor withdrawal in fibroblasts overproducingfructose 2,6-bisphosphate

Fructose 2,6-bisphosphate is a potent endogenous stimulator of glycolysis, A high aerobic glycolytic rate often correlates with increased cell prolife ration. To investigate this relationship, we have produced clonal cell line s of Rat-1 fibroblasts that stably express transgenes coding for 6-phosphof ructo-2-kinase, which catalyzes the synthesis of fructose 2,6-bisphosphate, or for fructose 2,6-bisphosphatase, which catalyzes its degradation. While serum deprivation in culture reduced the growth rate of control cells, it caused apoptosis in cells overproducing fructose 2,6-bisphosphate. Apoptosi s was inhibited by 5-amino-4-imidazolecarboxamide riboside, suggesting that 5'-AMP-activated protein kinase interferes with this phenomenon. (C) 1999 Federation of European Biochemical Societies.