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

FEBS Letters

Guzmán, Manuel¹  Velasco, Guillermo¹  Geelen, Math J.H²  Blázquez, Cristina¹ 

[1] Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain;Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands

关键词: AMP-activated protein kinase;    Apoptosis;    Ceramide;    Extracellular signal-regulated kinase;    Astrocyte;    ACC;    acetyl-CoA carboxylase;    AICAR;    5-aminoimidazole-4-carboxamide ribonucleoside;    AMPK;    AMP-activated protein kinase;    CPT-I;    carnitine palmitoyltransferase I;    ERK;    extracellular signal-regulated kinase;    SPT;    serine palmitoyltransferase;   

DOI  :  10.1016/S0014-5793(01)02089-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown