Changes in Differential Gene Expression in Fibroblast Cells from Patients with Triple A Syndrome under Oxidative Stress
Changes in Differential Gene Expression in Fibroblast Cells from Patients with Triple A Syndrome under Oxidative Stress
复制标题
DOI：
10.1055/s-0032-1331196
复制
发表时间：
2013-02-01
影响因子：
2.2
通讯作者：
Huebner, A.
中科院分区：
文献类型：
--
作者：
Koehler, K.;End, K.;Huebner, A.
三A综合征是一种罕见的常染色体隐性遗传病，由编码核孔蛋白ALADIN的AAAS基因突变引起。最近研究表明ALADIN在将不同的因子输入细胞核中起作用，这些因子防止细胞在氧化应激下DNA损伤和连续的细胞死亡。为了研究ALADIN缺陷或突变细胞在氧化应激下差异基因表达的变化，我们使用了三A综合征患者的成纤维细胞培养物，并将其与对照组进行了比较。对84个与氧化应激和抗氧化防御相关的基因的分析表明，有7个基因受到显著和差异的调控，即BCL 2/腺病毒E1 B 19 kD相互作用蛋白3（BNIP 3）、24-脱氢胆固醇还原酶（DHCR 24）、双特异性磷酸酶1（DUSP 1）、叉头盒M1（FOXM 1）、nudix型基序1（NUDT 1）、胰高血糖素-内过氧化物合酶2（PTGS 2）和清道夫受体A类成员3（SCARA 3）。在对照细胞中，百草枯处理后DHCR 24、FOXM 1、NUDT 1和SCARA 3的表达下降，而患者细胞中的表达没有显着变化。然而，患者细胞中SCARA 3和BNIP 3的基础表达显著高于对照细胞，而PTGS 2表达较少。此外，百草枯处理后，对照细胞中BNIP 3、DUSP 1和PTGS 2的表达显著增加，而患者细胞中DUSP 1和PTGS 2表达的增加显著减少。通过这项工作，我们证实了AAA患者的细胞显示出与氧化应激和抗氧化防御相关的基因的诱导或下调。
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.