Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells

FEBS Lett. 2002 Aug 28;526(1-3):38-42. doi: 10.1016/s0014-5793(02)03110-1.


The aim of this work was to study the effect of a sustained activation of AMP-activated protein kinase (AMPK) on liver cell survival. AMPK activation was achieved by incubating FTO2B cells with AICA-riboside, which is transformed into ZMP, an AMP analogue, or by adenoviral transfection of hepatocytes with a constitutively active form of AMPK. Prolonged AMPK activation triggered apoptosis and activated c-Jun N-terminal kinase (JNK) and caspase-3. Experiments with iodotubercidin, dicoumarol and z-VAD-fmk, which inhibited AMPK, JNK and caspase activation, respectively, supported the notion that prolonged AMPK activation in liver cells induces apoptosis through an activation pathway that involves JNK and caspase-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / metabolism
  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • JNK Mitogen-Activated Protein Kinases
  • Liver / cytology
  • Liver / enzymology
  • Liver / physiology*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Recombinant Proteins / metabolism
  • Ribonucleotides / metabolism
  • Transfection


  • Recombinant Proteins
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Cyclic AMP-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • AICA ribonucleotide