Abstract
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
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Oxidoreductases / metabolism
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Aminoimidazole Carboxamide / analogs & derivatives*
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Aminoimidazole Carboxamide / pharmacology*
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Animals
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Apoptosis*
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Cell Line, Tumor
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme Activation
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Hydrogen Peroxide / pharmacology
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Hypoglycemic Agents / pharmacology*
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Mice
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / metabolism*
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Oxidative Stress / drug effects*
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Oxidative Stress / physiology
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Ribonucleotides / pharmacology*
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Time Factors
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p38 Mitogen-Activated Protein Kinases
Substances
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Hypoglycemic Agents
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NF-kappa B
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Ribonucleotides
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Aminoimidazole Carboxamide
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Hydrogen Peroxide
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Aldehyde Oxidoreductases
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ethylmalonate-semialdehyde dehydrogenase
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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AICA ribonucleotide