Abstract
The triple A syndrome is a rare autosomal recessive disease caused by mutations in the AAAS gene, which encodes the nucleoporin ALADIN. Recently it was shown that ALADIN plays a role in the import of different factors into the nucleus, which prevent the cell from DNA damage and consecutive cell death under oxidative stress. In order to investigate the changes in differential gene expression in ALADIN-deficient or mutated cells under oxidative stress we used fibroblast cell cultures of triple A syndrome patients and compared these to controls. Analysis of 84 genes, which are associated with oxidative stress and antioxidant defense, showed that 7 genes were significantly and differentially regulated, namely BCL2/adenovirus E1B 19kD-interacting protein 3 (BNIP3), 24-dehydrocholesterol reductase (DHCR24), dual specificity phosphatase 1 (DUSP1), forkhead box M1 (FOXM1), nudix-type motif 1 (NUDT1), prostaglandin-endoperoxide synthase 2 (PTGS2), and scavenger receptor class A, member 3 (SCARA3). Whereas in control cells the expression of DHCR24, FOXM1, NUDT1, and SCARA3 was decreased after paraquat treatment, the expression did not change significantly in patient cells. However, the basal expression of SCARA3 and BNIP3 was significantly higher in patient cells than in controls whereas PTGS2 was less expressed. Furthermore, after paraquat treatment the expression of BNIP3, DUSP1, and PTGS2 was significantly increased in control cells while in patient cells the increase of DUSP1 and PTGS2 expression was significantly reduced. With this work we confirm that cells of triple A patients show an altered induction or downregulation of genes associated with oxidative stress and antioxidant defense.
Key words
ALADIN - nucleoporin - oxidative stress - PCR array
