The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes |
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Authors: | Blázquez C Geelen M J Velasco G Guzmán M |
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Affiliation: | Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain. |
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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. |
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