title: Pro-apoptotic activity of N-myc in activation-induced cell death of microglia.
abstract: Brain microglial cells are thought to undergo apoptosis following the exposure to inflammatory stimuli such as lipopolysaccharide (LPS) and IFNgamma, which is considered as an autoregulatory mechanism to control their own activation state. Here, we report that N-myc constitutes a novel apoptotic pathway of LPS/IFNgamma-activated microglia. The expression of N-myc was synergistically enhanced by LPS and IFNgamma in microglia. Tetracycline-based conditional expression of N-myc sensitized microglia to nitric oxide (NO)-induced apoptosis. Knockdown of N-myc expression using small interfering RNA (siRNA) attenuated LPS/IFNgamma-induced microglial apoptosis. An increase in N-myc expression, however, did not affect microglial production of NO or TNFalpha. The synergistic effect of LPS/IFNgamma on the microglial N-myc induction was mediated through Janus kinase (JAK)/STAT1 (signal transducer and activator of transcription 1) pathway. Taken together, LPS/IFNgamma-induced N-myc participated in the activation-induced cell death of microglia by sensitizing the cells to NO-induced apoptosis; however, N-myc did not influence the processes of inflammatory activation of microglia.
authors.affiliation: Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: Heasuk
authors.initials: H
authors.lastname: Lee
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D016259:Genes, myc / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000166:cytology* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D008070:Lipopolysaccharides; C489427:MYC protein, human; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D007371:Interferon-gamma