Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells.
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.
Hormone and Metabolic Research Unit, University of Louvain Medical School and Christian de Duve International Institute of Molecular and Cellular Pathology, Brussels, Belgium. delphine.meisse@horm.ucl.ac.be
Delphine
D
Meisse
Mark
M
Van de Casteele
Christophe
C
Beauloye
Isabelle
I
Hainault
Benjamin A
BA
Kefas
Mark H
MH
Rider
Fabienne
F
Foufelle
Louis
L
Hue
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism; D014162:Transfection
D011994:Recombinant Proteins; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017868:Cyclic AMP-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C031143:AICA ribonucleotide