Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines
Abstract Mitoplasticity occurs when mitochondria adapt to tolerate stressors. Previously we hypothesized that a subset of lymphoblastoid cell lines (LCLs) from children with autistic disorder (AD) show mitoplasticity (AD-A), presumably due to previous environmental exposures; another subset of AD LC...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-04821-3 |
| _version_ | 1819127346371756032 |
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| author | Richard Eugene Frye Shannon Rose Rebecca Wynne Sirish C. Bennuri Sarah Blossom Kathleen M. Gilbert Lynne Heilbrun Raymond F. Palmer |
| author_facet | Richard Eugene Frye Shannon Rose Rebecca Wynne Sirish C. Bennuri Sarah Blossom Kathleen M. Gilbert Lynne Heilbrun Raymond F. Palmer |
| author_sort | Richard Eugene Frye |
| collection | DOAJ |
| description | Abstract Mitoplasticity occurs when mitochondria adapt to tolerate stressors. Previously we hypothesized that a subset of lymphoblastoid cell lines (LCLs) from children with autistic disorder (AD) show mitoplasticity (AD-A), presumably due to previous environmental exposures; another subset of AD LCLs demonstrated normal mitochondrial activity (AD-N). To better understand mitoplasticity in the AD-A LCLs we examined changes in mitochondrial function using the Seahorse XF96 analyzer in AD and Control LCLs after exposure to trichloroacetaldehyde hydrate (TCAH), an in vivo metabolite of the environmental toxicant and common environmental pollutant trichloroethylene. To better understand the role of reactive oxygen species (ROS) in mitoplasticity, TCAH exposure was followed by acute exposure to 2,3-dimethoxy-1,4-napthoquinone (DMNQ), an agent that increases ROS. TCAH exposure by itself resulted in a decline in mitochondrial respiration in all LCL groups. This effect was mitigated when TCAH was followed by acute DMNQ exposure but this varied across LCL groups. DMNQ did not affect AD-N LCLs, while it neutralized the detrimental effect of TCAH in Control LCLs and resulted in a increase in mitochondrial respiration in AD-A LCLs. These data suggest that acute increases in ROS can activate mitochondrial protective pathways and that AD-A LCLs are better able to activate these protective pathways. |
| first_indexed | 2024-12-22T08:10:28Z |
| format | Article |
| id | doaj.art-8adb3ed2c3244654acf5122a3dc3096f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T08:10:28Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8adb3ed2c3244654acf5122a3dc3096f2022-12-21T18:33:02ZengNature PortfolioScientific Reports2045-23222017-06-017111410.1038/s41598-017-04821-3Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell LinesRichard Eugene Frye0Shannon Rose1Rebecca Wynne2Sirish C. Bennuri3Sarah Blossom4Kathleen M. Gilbert5Lynne Heilbrun6Raymond F. Palmer7Arkansas Children’s Research InstituteArkansas Children’s Research InstituteArkansas Children’s Research InstituteArkansas Children’s Research InstituteArkansas Children’s Research InstituteArkansas Children’s Research InstituteDepartment of Family and Community Medicine, University of Texas Health Science CenterDepartment of Family and Community Medicine, University of Texas Health Science CenterAbstract Mitoplasticity occurs when mitochondria adapt to tolerate stressors. Previously we hypothesized that a subset of lymphoblastoid cell lines (LCLs) from children with autistic disorder (AD) show mitoplasticity (AD-A), presumably due to previous environmental exposures; another subset of AD LCLs demonstrated normal mitochondrial activity (AD-N). To better understand mitoplasticity in the AD-A LCLs we examined changes in mitochondrial function using the Seahorse XF96 analyzer in AD and Control LCLs after exposure to trichloroacetaldehyde hydrate (TCAH), an in vivo metabolite of the environmental toxicant and common environmental pollutant trichloroethylene. To better understand the role of reactive oxygen species (ROS) in mitoplasticity, TCAH exposure was followed by acute exposure to 2,3-dimethoxy-1,4-napthoquinone (DMNQ), an agent that increases ROS. TCAH exposure by itself resulted in a decline in mitochondrial respiration in all LCL groups. This effect was mitigated when TCAH was followed by acute DMNQ exposure but this varied across LCL groups. DMNQ did not affect AD-N LCLs, while it neutralized the detrimental effect of TCAH in Control LCLs and resulted in a increase in mitochondrial respiration in AD-A LCLs. These data suggest that acute increases in ROS can activate mitochondrial protective pathways and that AD-A LCLs are better able to activate these protective pathways.https://doi.org/10.1038/s41598-017-04821-3 |
| spellingShingle | Richard Eugene Frye Shannon Rose Rebecca Wynne Sirish C. Bennuri Sarah Blossom Kathleen M. Gilbert Lynne Heilbrun Raymond F. Palmer Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines Scientific Reports |
| title | Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines |
| title_full | Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines |
| title_fullStr | Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines |
| title_full_unstemmed | Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines |
| title_short | Oxidative Stress Challenge Uncovers Trichloroacetaldehyde Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines |
| title_sort | oxidative stress challenge uncovers trichloroacetaldehyde hydrate induced mitoplasticity in autistic and control lymphoblastoid cell lines |
| url | https://doi.org/10.1038/s41598-017-04821-3 |
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