Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines
The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with au...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2015/573701 |
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| author | Shannon Rose Rebecca Wynne Richard E. Frye Stepan Melnyk S. Jill James |
| author_facet | Shannon Rose Rebecca Wynne Richard E. Frye Stepan Melnyk S. Jill James |
| author_sort | Shannon Rose |
| collection | DOAJ |
| description | The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction. |
| format | Article |
| id | doaj-art-d04a6da6b2664e7880c02f5677009c4f |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-d04a6da6b2664e7880c02f5677009c4f2025-02-03T01:22:44ZengWileyJournal of Toxicology1687-81911687-82052015-01-01201510.1155/2015/573701573701Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell LinesShannon Rose0Rebecca Wynne1Richard E. Frye2Stepan Melnyk3S. Jill James4Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR 72202, USADepartment of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR 72202, USADepartment of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR 72202, USADepartment of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR 72202, USADepartment of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital Research Institute, 13 Children’s Way, Slot 512-41B, Little Rock, AR 72202, USAThe association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction.http://dx.doi.org/10.1155/2015/573701 |
| spellingShingle | Shannon Rose Rebecca Wynne Richard E. Frye Stepan Melnyk S. Jill James Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines Journal of Toxicology |
| title | Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines |
| title_full | Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines |
| title_fullStr | Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines |
| title_full_unstemmed | Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines |
| title_short | Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines |
| title_sort | increased susceptibility to ethylmercury induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines |
| url | http://dx.doi.org/10.1155/2015/573701 |
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