title: The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Blázquez
authors.forename: M J
authors.initials: MJ
authors.lastname: Geelen
authors.forename: G
authors.initials: G
authors.lastname: Velasco
authors.forename: M
authors.initials: M
authors.lastname: Guzmán
mesh_terms: D055372:AMP-Activated Protein Kinases; D000217:Acyltransferases / Q000187:drug effects / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology; D051102:Serine C-Palmitoyltransferase; D013997:Time Factors
chemical_list: D002518:Ceramides; D005227:Fatty Acids; D009097:Multienzyme Complexes; D010168:Palmitates; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide