The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes

Fatty acids induce apoptosis in primary astrocytes by enhancing ceramide sy nthesis de novo, The possible role of the AR IP-activated protein kinase (A MPK) in the control of apoptosis was studied in this model. Long-term stimu lation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) p revented apoptosis, AICAR blunted fatty acid-mediated induction of serine p almitoyltransferase 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, Da ta indicate that AMPK may protect cells from apoptosis induced by stress st imuli. (C) 2001 Federation of European Bicohemical Societies. Published by Elsevier Science B.V. All rights reserved.