Abstract
The activity of hepatic carnitine palmitoyltransferase I (CPT-I) may be modulated by interactions with cytoskeletal components [Velasco et al. (1998) J. Biol. Chem. 273, 21497-21504]. We have studied whether the AMP-activated protein kinase (AMPK) is involved in this process. AMPK stimulated CPT-I in permeabilized hepatocytes but not in isolated liver mitochondria. In addition, AMPK abrogated the inhibition of CPT-I of isolated mitochondria induced by a cytoskeletal fraction. These two effects of AMPK were not evident when the kinase was inactivated by pretreatment with protein phosphatase 2C. Cytokeratins 8 and 18 were phosphorylated by AMPK in vitro and by incubation of intact hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside, a cell-permeable activator of AMPK. These results provide the first evidence that AMPK stimulates CPT-I by direct phosphorylation of cytoskeletal components.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Carnitine O-Palmitoyltransferase / metabolism*
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Carnitine O-Palmitoyltransferase / physiology
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Cell Membrane Permeability / drug effects
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Cells, Cultured
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Cytoskeleton / drug effects
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Cytoskeleton / metabolism*
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Enzyme Activation
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In Vitro Techniques
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Keratins / metabolism
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Liver / cytology
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Liver / drug effects
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Liver / enzymology*
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Malonyl Coenzyme A / metabolism
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Mitochondria, Liver / drug effects
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Mitochondria, Liver / enzymology
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Multienzyme Complexes / metabolism*
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Multienzyme Complexes / physiology
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Phosphorylation
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Protein Kinases / metabolism*
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Protein Kinases / physiology
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Protein Serine-Threonine Kinases*
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Rats
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Ribonucleotides / pharmacology
Substances
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Multienzyme Complexes
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Ribonucleotides
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Aminoimidazole Carboxamide
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Malonyl Coenzyme A
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Keratins
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Carnitine O-Palmitoyltransferase
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Protein Kinases
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Protein Serine-Threonine Kinases
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AMP-Activated Protein Kinases
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AICA ribonucleotide