1. Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells
- Author
-
Isabelle Hainault, Christophe Beauloye, Benjamin A. Kefas, Mark H. Rider, Louis Hue, D. Meisse, Fabienne Foufelle, Mark Van de Casteele, and Pathologic Biochemistry and Physiology
- Subjects
Endocrinology, Diabetes and Metabolism ,Biophysics ,Liver/cytology ,Apoptosis ,Mitogen-activated protein kinase kinase ,Transfection ,Cyclic AMP-Dependent Protein Kinases/metabolism ,Biochemistry ,Cell Line ,MAP2K7 ,Structural Biology ,Aminoimidazole Carboxamide/analogs & derivatives ,Genetics ,Animals ,ASK1 ,Hepatocyte ,Molecular Biology ,c-Jun N-terminal kinase ,Ribonucleotides/metabolism ,Recombinant Proteins/metabolism ,MAP kinase kinase kinase ,AMP-activated protein kinase ,Chemistry ,Liver cell ,JNK Mitogen-Activated Protein Kinases ,AMPK ,Apoptosis/physiology ,Cell Biology ,Ribonucleotides ,Aminoimidazole Carboxamide ,Cyclic AMP-Dependent Protein Kinases ,Protein kinase R ,AICA-riboside ,Recombinant Proteins ,Cell biology ,Enzyme Activation ,Liver ,Cyclin-dependent kinase 9 ,Mitogen-Activated Protein Kinases ,Mitogen-Activated Protein Kinases/metabolism - Abstract
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.
- Full Text
- View/download PDF