Abstract
Fatty acids induce apoptosis in primary astrocytes by enhancing ceramide synthesis de novo. The possible role of the AMP-activated protein kinase (AMPK) in the control of apoptosis was studied in this model. Long-term stimulation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevented apoptosis. AICAR blunted fatty acid-mediated induction of serine palmitoyltransferase and ceramide synthesis de novo, without affecting fatty acid synthesis and oxidation. Prevention of ceramide accumulation by AICAR led to a concomitant blockade of the Raf-1/extracellular signal-regulated kinase cascade, which selectively mediates fatty acid-induced apoptosis. Data indicate that AMPK may protect cells from apoptosis induced by stress stimuli.
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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Acyltransferases / drug effects
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Acyltransferases / metabolism
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Aminoimidazole Carboxamide / analogs & derivatives*
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Apoptosis*
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Cell Survival / drug effects
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Cells, Cultured
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Ceramides / biosynthesis*
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Enzyme Activation / drug effects
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Fatty Acids / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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Multienzyme Complexes / metabolism*
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Palmitates / pharmacology
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-raf / metabolism
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Rats
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Rats, Wistar
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Ribonucleotides / pharmacology
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Serine C-Palmitoyltransferase
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Time Factors
Substances
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Ceramides
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Fatty Acids
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Multienzyme Complexes
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Palmitates
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Ribonucleotides
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Aminoimidazole Carboxamide
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Acyltransferases
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Serine C-Palmitoyltransferase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinases
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AMP-Activated Protein Kinases
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AICA ribonucleotide