title: Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades.
abstract: Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to nitric oxide induced neuronal injury by global transcriptomic profiling. Microarray analyses were undertaken on RNA from murine primary cortical neurons treated with the nitric oxide generator DETA-NONOate (NOC-18, 0.5 mM) for 8-24 hrs. Biological pathway analysis focused upon 3672 gene probes which demonstrated at least a ±1.5-fold expression in a minimum of one out of three time-points and passed statistical analysis (one-way anova, P < 0.05). Numerous enriched processes potentially determining nitric oxide mediated neuronal injury were identified from the transcriptomic profile: cell death, developmental growth and survival, cell cycle, calcium ion homeostasis, endoplasmic reticulum stress, oxidative stress, mitochondrial homeostasis, ubiquitin-mediated proteolysis, and GSH and nitric oxide metabolism. Our detailed time-course study of nitric oxide induced neuronal injury allowed us to provide the first time a holistic description of the temporal sequence of cellular events contributing to nitrergic injury. These data form a foundation for the development of screening platforms and define targets for intervention in nitric oxide neuropathologies where nitric oxide mediated injury is causative.
authors.affiliation: Key Laboratory of Biogeology and Environmental Geology of the Ministry of Education, China University of Geosciences, Wuhan, China.
authors.forename: Zhao Feng
authors.initials: ZF
authors.lastname: Peng
authors.forename: Minghui Jessica
authors.initials: MJ
authors.lastname: Chen
authors.forename: Jayapal
authors.initials: J
authors.lastname: Manikandan
authors.forename: Alirio J
authors.initials: AJ
authors.lastname: Melendez
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Françoise
authors.initials: F
authors.lastname: Russo-Marie
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.forename: Philip M
authors.initials: PM
authors.lastname: Beart
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
authors.forename: Nam Sang
authors.initials: NS
authors.lastname: Cheung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase