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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
journal contributionposted on 2023-05-17, 17:50 authored by Yap, YW, Chen, MJ, Peng, ZF, Manikandan, J, Ng, JMJ, Llanos, RM, La Fontaine, S, Beart, PM, Cheung, NS
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 Â±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. Â© 2012 Elsevier Ltd. All rights reserved.
Publication titleNeurochemistry International
Department/SchoolMenzies Institute for Medical Research
PublisherPergamon-Elsevier Science Ltd
Place of publicationThe Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1Gb
Rights statementCopyright 2012 Elsevier Ltd.