Antioxidants partially restore glutamate transport defect in leber hereditary optic neuropathy cybrids
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss resulting from retinal ganglion cell degeneration. Despite the important role of respiratory chain deficiency and oxidative stress induced by mtDNA point mutations affecting complex I, excitotoxic injury...
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Published in | Journal of neuroscience research Vol. 86; no. 15; pp. 3331 - 3337 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.11.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Leber hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss resulting from retinal ganglion cell degeneration. Despite the important role of respiratory chain deficiency and oxidative stress induced by mtDNA point mutations affecting complex I, excitotoxic injury has been postulated as a concurrent pathogenic factor. We used transmitochondrial cybrid cell lines constructed using enucleated fibroblasts from three LHON probands carrying the most severe 3460/ND1 mutation and three controls as mitochondria donors, and the osteosarcoma‐derived mtDNA‐less cells, to study the possible efficacy of two selected antioxidant compounds in preventing glutamate uptake reduction previously observed in LHON cybrids. We demonstrated that two antioxidants, Trolox and decylubiquinone, partially restore glutamate transport impairment occurring in LHON cybrids. Rotenone, a classic complex I inhibitor, did not worsen the glutamate uptake defect present in LHON cybrids under basal conditions but significantly reduced glutamate transport in control cybrids. Furthermore, we observed that LHON cybrids showed an increased protein carbonylation under basal conditions, not further affected by rotenone and partially counteracted by antioxidants. Our findings strengthen the hypothesis that the complex I defect associated with LHON causes free radical overproduction, which is responsible for glutamate transport inhibition. We suggest that selected antioxidants may be clinically tested in LHON patients and relatives to restore glutamate uptake defect caused by LHON‐associated free radical overproduction. © 2008 Wiley‐Liss, Inc. |
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Bibliography: | ark:/67375/WNG-N7Q8WJ19-L istex:8AC6684F1DFCDD31FBD55BC874A55C8163DAA1DC ArticleID:JNR21773 Ricerca Finalizzata 2004 - No. 0011549 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0360-4012 1097-4547 |
DOI: | 10.1002/jnr.21773 |