Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON)
| Autor: | Beretta, S, Wood, JPM, Derham, B, SALA, GESSICA, TREMOLIZZO, LUCIO, Osborne, NN, FERRARESE, CARLO |
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| Přispěvatelé: | Beretta, S, Wood, J, Derham, B, Sala, G, Tremolizzo, L, Ferrarese, C, Osborne, N |
| Rok vydání: | 2005 |
| Předmět: |
Retinal Ganglion Cells
Free Radicals Glutamic Acid Optic Atrophy Hereditary Leber complex 1 GLAST Retina Rotenone Animals Rats Wistar Cells Cultured MED/26 - NEUROLOGIA Neurons reactive oxygen specie Electron Transport Complex I leber hereditary optic neuropathy (LHON) Cell Death Dose-Response Relationship Drug Uncoupling Agents Mitochondria Rats Excitatory Amino Acid Transporter 1 Oxidative Stress Animals Newborn Lipid Peroxidation Energy Metabolism excitotoxicity Neuroglia |
| Zdroj: | Neurobiology of disease. 24(2) |
| ISSN: | 0969-9961 |
| Popis: | 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 Mfiller 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 Mfiller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex 1-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON. (c) 2006 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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