Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.

Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.

Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the path...

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Main Authors: Simone Beretta, John P.M. Wood, Barry Derham, Gessica Sala, Lucio Tremolizzo, Carlo Ferrarese, Neville N. Osborne
Format: Article
Language:English
Published: Elsevier 2006-11-01
Series:Neurobiology of Disease
Subjects:
Complex I
Leber hereditary optic neuropathy (LHON)
Reactive oxygen species
Excitotoxicity
GLAST
Retina
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996106001677
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spelling doaj-f394c48bf4c24d46b90cba82815434692021-03-20T04:53:15ZengElsevierNeurobiology of Disease1095-953X2006-11-01242308317Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.Simone Beretta0John P.M. Wood1Barry Derham2Gessica Sala3Lucio Tremolizzo4Carlo Ferrarese5Neville N. Osborne6Department of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, Via Cadore 48, 20052 Monza (MI), Italy; Corresponding author. Fax: +39 02 6448 8108.Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW, UKDepartment of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UKDepartment of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, Via Cadore 48, 20052 Monza (MI), ItalyDepartment of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, Via Cadore 48, 20052 Monza (MI), ItalyDepartment of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, Via Cadore 48, 20052 Monza (MI), ItalyNuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW, UKLeber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON.http://www.sciencedirect.com/science/article/pii/S0969996106001677Complex ILeber hereditary optic neuropathy (LHON)Reactive oxygen speciesExcitotoxicityGLASTRetina
collection DOAJ
language English
format Article
sources DOAJ
author Simone Beretta
John P.M. Wood
Barry Derham
Gessica Sala
Lucio Tremolizzo
Carlo Ferrarese
Neville N. Osborne
spellingShingle Simone Beretta
John P.M. Wood
Barry Derham
Gessica Sala
Lucio Tremolizzo
Carlo Ferrarese
Neville N. Osborne
Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
Neurobiology of Disease
Complex I
Leber hereditary optic neuropathy (LHON)
Reactive oxygen species
Excitotoxicity
GLAST
Retina
author_facet Simone Beretta
John P.M. Wood
Barry Derham
Gessica Sala
Lucio Tremolizzo
Carlo Ferrarese
Neville N. Osborne
author_sort Simone Beretta
title Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
title_short Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
title_full Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
title_fullStr Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
title_full_unstemmed Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
title_sort partial mitochondrial complex i inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures.
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2006-11-01
description Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON.
topic Complex I
Leber hereditary optic neuropathy (LHON)
Reactive oxygen species
Excitotoxicity
GLAST
Retina
url http://www.sciencedirect.com/science/article/pii/S0969996106001677
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