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Gene expression profiling of rotenone-mediated cortical neuronal death: Evidence for inhibition of ubiquitin-proteasome system and autophagy-lysosomal pathway, and dysfunction of mitochondrial and calcium signaling

Citation

Yap, YW and Chen, MJ and Peng, ZF and Manikandan, J and Ng, JMJ and Llanos, RM and La Fontaine, S and Beart, PM and Cheung, NS, Gene expression profiling of rotenone-mediated cortical neuronal death: Evidence for inhibition of ubiquitin-proteasome system and autophagy-lysosomal pathway, and dysfunction of mitochondrial and calcium signaling, Neurochemistry International, 62, (5) pp. 653-663. ISSN 0197-0186 (2013) [Refereed Article]

Copyright Statement

Copyright 2012 Elsevier Ltd.

DOI: doi:10.1016/j.neuint.2012.11.011

Abstract

Mitochondrial dysfunction and oxidative stress are currently considered two key mechanisms contributing to pathobiology in neurodegenerative conditions. The current study investigated the temporal molecular events contributing to programmed cell death after treatment with the mitochondrial complex I inhibitor rotenone. Microarray analysis was performed using cultured neocortical neurons treated with 10 nM rotenone for 8, 15, and 24 h. Genes showing at least ±1.2-fold change in expression at one time point were considered significant. Transcriptomic analysis of the 4178 genes probes revealed major changes to nine biological processes, including those eliciting mitochondrial dysfunction, activation of calcium signaling, increased expression of apoptotic genes, and downplay of chaperones/co-chaperones, ubiquitin-proteasome system and autophagy. These data define targets for intervention where mitochondrial complex I dysfunction plays a substantial role, most notably Parkinson's disease. © 2012 Elsevier Ltd. All rights reserved.

Item Details

Item Type:Refereed Article
Keywords:Rotenone, Oxidative stress, Mitochondria complex 1 inhibition, Programmed cell death, Protein handling, Neurodegeneration
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:Ng, JMJ (Mr Jeremy Ng)
Author:Cheung, NS (Dr Nam Cheung)
ID Code:84616
Year Published:2013
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-05-23
Last Modified:2014-04-17
Downloads:0

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