Compensation for chronic oxidative stress in ALADIN null mice
Mutations in the AAAS gene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. Triple A patients present with a characteristic phenotype including alacrima, achalasia and adrenal insufficiency. Patient fibroblasts show increased levels of ox...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-01-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/7/1/bio030742 |
| _version_ | 1818671627766857728 |
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| author | Ramona Jühlen Mirko Peitzsch Sebastian Gärtner Dana Landgraf Graeme Eisenhofer Angela Huebner Katrin Koehler |
| author_facet | Ramona Jühlen Mirko Peitzsch Sebastian Gärtner Dana Landgraf Graeme Eisenhofer Angela Huebner Katrin Koehler |
| author_sort | Ramona Jühlen |
| collection | DOAJ |
| description | Mutations in the AAAS gene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. Triple A patients present with a characteristic phenotype including alacrima, achalasia and adrenal insufficiency. Patient fibroblasts show increased levels of oxidative stress, and several in vitro studies have demonstrated that the nucleoporin ALADIN is involved in both the cellular oxidative stress response and adrenal steroidogenesis. It is known that ALADIN knock-out mice lack a phenotype resembling human triple A syndrome. The objective of this study was to determine whether the application of chronic oxidative stress by ingestion of paraquat would generate a triple A-like phenotype in ALADIN null mice. Adult male mice were fed either a paraquat (0.25 g/kg diet) or control diet for 11 days. After application of chronic oxidative stress, ALADIN knock-out mice presented with an unexpected compensated glutathione metabolism, but lacked a phenotype resembling human triple A syndrome. We did not observe increased levels of oxidative stress and alterations in adrenal steroidogenesis in mice depleted for ALADIN. This study stresses the species-specific role of the nucleoporin ALADIN, which in mice involves a novel compensatory mechanism for regulating the cellular glutathione redox response. |
| first_indexed | 2024-12-17T07:27:01Z |
| format | Article |
| id | doaj.art-c0d312fad5634db7a8a0f56140e14cd5 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T07:27:01Z |
| publishDate | 2018-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-c0d312fad5634db7a8a0f56140e14cd52022-12-21T21:58:35ZengThe Company of BiologistsBiology Open2046-63902018-01-017110.1242/bio.030742030742Compensation for chronic oxidative stress in ALADIN null miceRamona Jühlen0Mirko Peitzsch1Sebastian Gärtner2Dana Landgraf3Graeme Eisenhofer4Angela Huebner5Katrin Koehler6 Klinik und Poliklinik für Kinder-und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany Institut für Klinische Chemie und Laboratoriumsmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany Institut für Radiopharmazeutische Krebsforschung, Helmholtz-Zentrum Dresden-Rossendorf, Dresden 01328, Germany Klinik und Poliklinik für Kinder-und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany Institut für Klinische Chemie und Laboratoriumsmedizin, Medizinische Klinik und Poliklinik III, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany Klinik und Poliklinik für Kinder-und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany Klinik und Poliklinik für Kinder-und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany Mutations in the AAAS gene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. Triple A patients present with a characteristic phenotype including alacrima, achalasia and adrenal insufficiency. Patient fibroblasts show increased levels of oxidative stress, and several in vitro studies have demonstrated that the nucleoporin ALADIN is involved in both the cellular oxidative stress response and adrenal steroidogenesis. It is known that ALADIN knock-out mice lack a phenotype resembling human triple A syndrome. The objective of this study was to determine whether the application of chronic oxidative stress by ingestion of paraquat would generate a triple A-like phenotype in ALADIN null mice. Adult male mice were fed either a paraquat (0.25 g/kg diet) or control diet for 11 days. After application of chronic oxidative stress, ALADIN knock-out mice presented with an unexpected compensated glutathione metabolism, but lacked a phenotype resembling human triple A syndrome. We did not observe increased levels of oxidative stress and alterations in adrenal steroidogenesis in mice depleted for ALADIN. This study stresses the species-specific role of the nucleoporin ALADIN, which in mice involves a novel compensatory mechanism for regulating the cellular glutathione redox response.http://bio.biologists.org/content/7/1/bio030742ALADINOxidative stressParaquatRedox homeostasisTriple A syndrome |
| spellingShingle | Ramona Jühlen Mirko Peitzsch Sebastian Gärtner Dana Landgraf Graeme Eisenhofer Angela Huebner Katrin Koehler Compensation for chronic oxidative stress in ALADIN null mice Biology Open ALADIN Oxidative stress Paraquat Redox homeostasis Triple A syndrome |
| title | Compensation for chronic oxidative stress in ALADIN null mice |
| title_full | Compensation for chronic oxidative stress in ALADIN null mice |
| title_fullStr | Compensation for chronic oxidative stress in ALADIN null mice |
| title_full_unstemmed | Compensation for chronic oxidative stress in ALADIN null mice |
| title_short | Compensation for chronic oxidative stress in ALADIN null mice |
| title_sort | compensation for chronic oxidative stress in aladin null mice |
| topic | ALADIN Oxidative stress Paraquat Redox homeostasis Triple A syndrome |
| url | http://bio.biologists.org/content/7/1/bio030742 |
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