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

FEBS Lett. 2001 Feb 2;489(2-3):149-53. doi: 10.1016/s0014-5793(01)02089-0.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Acyltransferases / drug effects
  • Acyltransferases / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Apoptosis*
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Ceramides / biosynthesis*
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Multienzyme Complexes / metabolism*
  • Palmitates / pharmacology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-raf / metabolism
  • Rats
  • Rats, Wistar
  • Ribonucleotides / pharmacology
  • Serine C-Palmitoyltransferase
  • Time Factors

Substances

  • Ceramides
  • Fatty Acids
  • Multienzyme Complexes
  • Palmitates
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Acyltransferases
  • Serine C-Palmitoyltransferase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide