Compensation for chronic oxidative stress in ALADIN null mice

Biology Open

Mirko Peitzsch¹  Graeme Eisenhofer²  Sebastian Gärtner³  Angela Huebner⁴  Dana Landgraf⁴  Katrin Koehler⁴  Ramona Jühlen⁴ 

[1] Institut für Klinische Chemie und Laboratoriumsmedizin, 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;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;

关键词: ALADIN;    Oxidative stress;    Paraquat;    Redox homeostasis;    Triple A syndrome;   

DOI  :  10.1242/bio.030742

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown