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

• Published in: FEBS letters 2002-08, Vol.526 (1), p.38-42
• Main Authors: Meisse, Delphine, Van de Casteele, Mark, Beauloye, Christophe, Hainault, Isabelle, Kefas, Benjamin A, Rider, Mark H, Foufelle, Fabienne, Hue, Louis
• Format: Article
• Language: English
• Subjects: AICA-riboside; AICA-riboside, 5-aminoimidazole-4-carboxamide-riboside; Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - metabolism; AMP-activated protein kinase; AMPK, AMP-activated protein kinase; Animals; Apoptosis; Apoptosis - physiology; c-Jun N-terminal kinase; Cell Line; Cyclic AMP-Dependent Protein Kinases - metabolism; Enzyme Activation; Hepatocyte; JNK Mitogen-Activated Protein Kinases; JNK, c-Jun N-terminal kinase; Liver - cytology; Liver - enzymology; Liver - physiology; Mitogen-Activated Protein Kinases - metabolism; Recombinant Proteins - metabolism; Ribonucleotides - metabolism; Transfection
• ISSN: 0014-5793; 1873-3468
• 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.