Effect of Insulin on Oxidative Stress and Caspase-3 Activity in a Cellular Model of Huntington's Disease

Abstract

Event Abstract Back to Event Effect of Insulin on Oxidative Stress and Caspase-3 Activity in a Cellular Model of Huntington's Disease A. I. Duarte1*, M. Ribeiro1, Ana Cristina-Rego1 and C. R. Oliveira1 1 University of Coimbra, Center for Neurosciences & Cell Biology, Portugal Huntington’s disease (HD) is the most prevalent polyglutamine expansion disease, characterized by motor and psychiatric disturbances. HD is caused by an expansion of CAG triplet in the exon 1 of the IT15 gene, encoding huntingtin (Htt). Pathologically, HD is characterized by striatal and cortical neuronal loss, which may involve metabolic abnormalities and formation of reactive oxygen species (ROS). Although we recently demonstrated that insulin significantly protects oxidized neurons, little is known about its role in HD. Thus, in this study we analysed the protective effect of insulin against neuronal death associated with high glucose levels, mitochondrial complex II inhibition and oxidative stress in a cellular model of HD. We used immortalized striatal progenitor cell lines derived from knock-in mice, expressing endogenous Htt with 7 (Q7) or 111 (Q111) glutamines. These cell lines were pretreated with insulin before induction of hyperglycemia with D-glucose, inhibition of mitochondrial complex II with 3-nitropropionic acid (3-NP) or induction of oxidative stress with hydrogen peroxide (H2O2) or staurosporine (STS). Cell viability, caspase-3 activation and ROS formation were determined by the Alamar blue reduction assay, cleavage of fluorimetric DEVD-AFC substrate and dihydrodichlorofluorescein-diacetate fluorescence, respectively. We observed a significant decrease in Q7 and Q111 cell viability upon exposure to stress inducers. Although treatment with insulin prevented almost completely the decrease in Q7 cells’ viability, it only partially restored the viability of Q111 striatal cells. Furthermore, insulin protected both cell lines against increased activation of caspase-3. Interestingly, insulin prevented ROS formation only in Q111 cells. These results suggest that insulin has a neuroprotective role against hyperglycemia, mitochondrial complex II inhibition and oxidative stress, and may thus constitute a promising therapeutic agent against striatal neurodegeneration associated with HD.Supported by Fundação para a Ciência e a Tecnologia (POCI 2010) and Fundo Social Europeu (SFRH/BPD/26872/2006). Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neurodegenerative Disorders Citation: Duarte AI, Ribeiro M, Cristina-Rego A and Oliveira CR (2009). Effect of Insulin on Oxidative Stress and Caspase-3 Activity in a Cellular Model of Huntington's Disease. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.070 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Aug 2009; Published Online: 07 Aug 2009. * Correspondence: A. I Duarte, University of Coimbra, Center for Neurosciences & Cell Biology, Alicante, Portugal, ana.duarte@cnc.uc.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers A. I Duarte M. Ribeiro Ana Cristina-Rego C. R Oliveira Google A. I Duarte M. Ribeiro Ana Cristina-Rego C. R Oliveira Google Scholar A. I Duarte M. Ribeiro Ana Cristina-Rego C. R Oliveira PubMed A. I Duarte M. Ribeiro Ana Cristina-Rego C. R Oliveira Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.