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

FEBS Lett. 1999 Apr 9;448(2-3):239-43. doi: 10.1016/s0014-5793(99)00387-7.

Abstract

Fructose 2,6-bisphosphate is a potent endogenous stimulator of glycolysis. A high aerobic glycolytic rate often correlates with increased cell proliferation. To investigate this relationship, we have produced clonal cell lines of Rat-1 fibroblasts that stably express transgenes coding for 6-phosphofructo-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. Apoptosis was inhibited by 5-amino-4-imidazolecarboxamide riboside, suggesting that 5'-AMP-activated protein kinase interferes with this phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Animals
  • Apoptosis*
  • Bromodeoxyuridine / metabolism
  • Dose-Response Relationship, Drug
  • Fibroblasts / physiology*
  • Fructosediphosphates / biosynthesis*
  • Glycolysis
  • Growth Substances / physiology*
  • Multienzyme Complexes / metabolism
  • Mutagenesis, Site-Directed
  • Phosphofructokinase-2
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Ribonucleotides
  • Time Factors
  • Transfection

Substances

  • Fructosediphosphates
  • Growth Substances
  • Multienzyme Complexes
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • fructose 2,6-diphosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • Phosphofructokinase-2
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Bromodeoxyuridine