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

Zhao Feng Peng¹  Minghui Jessica Chen⁶  Jayapal Manikandan⁸  Alirio J. Melendez⁸  Guanghou Shui⁷  Françoise Russo-Marie²  Matthew Whiteman⁴  Philip M. Beart⁵  Philip K. Moore³ 

[1] Key Laboratory of Biogeology and Environmental Geology of the Ministry of Education, China University of Geosciences, Wuhan, China;Institut Cochin, Paris, France;Pharmaceutical Science Division, King's College, London, UK;Peninsula Medical School, University of Exeter, St. Luke's Campus, Exeter, Devon, UK;Department of Pharmacology, Florey Neurosciences Institutes, University of Melbourne, Parkville, VIC, Australia;Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia;Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;Department of Physiology Yong Loo Lin School of Medicine, National University of Singapore, Singapore

关键词: nitric oxide;    neuronal injury;    oxidative stress;    microarray;    reactive oxygen species;    reactive nitrogen species;   

DOI  :  10.1111/j.1582-4934.2011.01288.x

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd