title: 5-Aminoimidazole-4-carboxamide-ribonucleoside enhances oxidative stress-induced apoptosis through activation of nuclear factor-kappaB in mouse Neuro 2a neuroblastoma cells.
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.
authors.affiliation: Department of Biochemistry, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-ku, Seoul 130-701, South Korea.
authors.forename: Joo Eun
authors.initials: JE
authors.lastname: Jung
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Cho
authors.forename: Hyung Hwan
authors.initials: HH
authors.lastname: Baik
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012265:Ribonucleotides / Q000494:pharmacology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D007004:Hypoglycemic Agents; D016328:NF-kappa B; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D006861:Hydrogen Peroxide; D000445:Aldehyde Oxidoreductases; C050832:ethylmalonate-semialdehyde dehydrogenase; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C031143:AICA ribonucleotide