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Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades

Citation

Peng, ZF and Chen, MJ and Manikandan, J and Melendez, AJ and Shui, G and Russo-Marie, F and Whiteman, M and Beart, PM and Moore, PK and Cheung, NS, Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades, Journal of Cellular and Molecular Medicine (Online), 16, (1) pp. 41-58. ISSN 1582-4934 (2012) [Refereed Article]

Copyright Statement

Copyright 2011 The Authors

DOI: doi:10.1111/j.1582-4934.2011.01288.x

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.

Item Details

Item Type:Refereed Article
Keywords:nitric oxide, neuronal injury, oxidative stress, microarray, reactive oxygen species; reactive nitrogen species
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Chen, MJ (Ms Minghui Chen)
Author:Cheung, NS (Dr Nam Cheung)
ID Code:80030
Year Published:2012
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-10-17
Last Modified:2013-04-17
Downloads:0

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