Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model
<p>Abstract</p> <p>Background</p> <p>Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-07-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://www.biomedcentral.com/1471-2202/13/86 |
| _version_ | 1818498436153999360 |
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| author | Ajayi Abiodun Yu Xin Lindberg Staffan Langel Ülo Ström Anna-Lena |
| author_facet | Ajayi Abiodun Yu Xin Lindberg Staffan Langel Ülo Ström Anna-Lena |
| author_sort | Ajayi Abiodun |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the polyQ protein and induction of oxidative stress. However, the exact mechanism(s) of toxicity is still unclear.</p> <p>Results</p> <p>In this study we show that expression of polyQ expanded ATXN7 in a novel stable inducible cell model first results in a concomitant increase in ROS levels and aggregation of the disease protein and later cellular toxicity. The increase in ROS could be completely prevented by inhibition of NADPH oxidase (NOX) complexes suggesting that ATXN7 directly or indirectly causes oxidative stress by increasing superoxide anion production from these complexes. Moreover, we could observe that induction of mutant ATXN7 leads to a decrease in the levels of catalase, a key enzyme in detoxifying hydrogen peroxide produced from dismutation of superoxide anions. This could also contribute to the generation of oxidative stress. Most importantly, we found that treatment with a general anti-oxidant or inhibitors of NOX complexes reduced both the aggregation and toxicity of mutant ATXN7. In contrast, ATXN7 aggregation was aggravated by treatments promoting oxidative stress.</p> <p>Conclusion</p> <p>Our results demonstrates that oxidative stress contributes to ATXN7 aggregation as well as toxicity and show that anti-oxidants or NOX inhibition can ameliorate mutant ATXN7 toxicity.</p> |
| first_indexed | 2024-12-10T18:58:48Z |
| format | Article |
| id | doaj.art-10af711ac55647b587a5c203c9cc0b7f |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-10T18:58:48Z |
| publishDate | 2012-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-10af711ac55647b587a5c203c9cc0b7f2022-12-22T01:37:04ZengBMCBMC Neuroscience1471-22022012-07-011318610.1186/1471-2202-13-86Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) modelAjayi AbiodunYu XinLindberg StaffanLangel ÜloStröm Anna-Lena<p>Abstract</p> <p>Background</p> <p>Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the polyQ protein and induction of oxidative stress. However, the exact mechanism(s) of toxicity is still unclear.</p> <p>Results</p> <p>In this study we show that expression of polyQ expanded ATXN7 in a novel stable inducible cell model first results in a concomitant increase in ROS levels and aggregation of the disease protein and later cellular toxicity. The increase in ROS could be completely prevented by inhibition of NADPH oxidase (NOX) complexes suggesting that ATXN7 directly or indirectly causes oxidative stress by increasing superoxide anion production from these complexes. Moreover, we could observe that induction of mutant ATXN7 leads to a decrease in the levels of catalase, a key enzyme in detoxifying hydrogen peroxide produced from dismutation of superoxide anions. This could also contribute to the generation of oxidative stress. Most importantly, we found that treatment with a general anti-oxidant or inhibitors of NOX complexes reduced both the aggregation and toxicity of mutant ATXN7. In contrast, ATXN7 aggregation was aggravated by treatments promoting oxidative stress.</p> <p>Conclusion</p> <p>Our results demonstrates that oxidative stress contributes to ATXN7 aggregation as well as toxicity and show that anti-oxidants or NOX inhibition can ameliorate mutant ATXN7 toxicity.</p>http://www.biomedcentral.com/1471-2202/13/86Ataxin-7NADPH oxidase complexNeurodegenerationOxidative stressPolyglutamineSCA7 |
| spellingShingle | Ajayi Abiodun Yu Xin Lindberg Staffan Langel Ülo Ström Anna-Lena Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model BMC Neuroscience Ataxin-7 NADPH oxidase complex Neurodegeneration Oxidative stress Polyglutamine SCA7 |
| title | Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model |
| title_full | Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model |
| title_fullStr | Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model |
| title_full_unstemmed | Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model |
| title_short | Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model |
| title_sort | expanded ataxin 7 cause toxicity by inducing ros production from nadph oxidase complexes in a stable inducible spinocerebellar ataxia type 7 sca7 model |
| topic | Ataxin-7 NADPH oxidase complex Neurodegeneration Oxidative stress Polyglutamine SCA7 |
| url | http://www.biomedcentral.com/1471-2202/13/86 |
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