5-Aminoimidazole-4-carboxamide-ribonucleoside enhances oxidative stress-induced apoptosis through activation of nuclear factor-kappaB in mouse Neuro 2a neuroblastoma cells

Neurosci Lett. 2004 Jan 16;354(3):197-200. doi: 10.1016/j.neulet.2003.10.012.


AMP-activated protein kinase (AMPK) was recently suggested to have a pro-apoptotic effect although its primary function is believed to mediate cellular adaptation to metabolic stresses. Here, we investigated the effect of the AMPK activator 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR) on oxidative stress-induced apoptosis using mouse Neuro 2a neuroblastoma cells. H2O2-induced apoptosis was increased by AMPK activation, either with AICAR pretreatment or with overexpression of active AMPK. AICAR also induced nuclear factor-kappaB (NF-kappaB) activation along with activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Correlation between NF-kappaB activation and the AICAR-enhanced apoptotic cell death was observed. In addition, NF-kappaB inhibitor SN50 prevented the augmented cell death by AICAR. Thus, our data suggest that NF-kappaB mediates the pro-apoptotic effect of AICAR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Oxidoreductases / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology*
  • Animals
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Activation
  • Hydrogen Peroxide / pharmacology
  • Hypoglycemic Agents / pharmacology*
  • Mice
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Ribonucleotides / pharmacology*
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases


  • Hypoglycemic Agents
  • NF-kappa B
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Hydrogen Peroxide
  • Aldehyde Oxidoreductases
  • ethylmalonate-semialdehyde dehydrogenase
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • AICA ribonucleotide