Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.
PLoS One. 2018 Apr 2;13(4):e0195388. doi: 10.1371/journal.pone.0195388. eCollection 2018.
Ataxia telangiectasia (A-T) is an incurable and rare hereditary syndrome. In recent times, treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this condition, but the molecular mechanism of action of these analogues remains unknown. Hence, the aim of this study was to gain insight into the molecular mechanism of action of glucocorticoid analogues in the treatment of A-T by investigating the role of Dexamethasone (Dexa) in A-T lymphoblastoid cell lines. We used 2DE and tandem MS to identify proteins that were influenced by the drug in A-T cells but not in healthy cells. Thirty-four proteins were defined out of a total of 746±63. Transcriptome analysis was performed by microarray and showed the differential expression of 599 A-T and 362 wild type (WT) genes and a healthy un-matching between protein abundance and the corresponding gene expression variation. The proteomic and transcriptomic profiles allowed the network pathway analysis to pinpoint the biological and molecular functions affected by Dexamethasone in Dexa-treated cells. The present integrated study provides evidence of the molecular mechanism of action of Dexamethasone in an A-T cellular model but also the broader effects of the drug in other tested cell lines.
共济失调毛细血管扩张症（A-T）是一种无法治愈的罕见遗传性综合征。近年来，糖皮质激素类似物的治疗已被证明可以改善这种疾病的神经症状，但这些类似物的作用机制尚不清楚。因此，本研究旨在通过研究地塞米松（Dexa）在 A-T 淋巴母细胞系中的作用，深入了解糖皮质激素类似物治疗 A-T 的作用机制。我们使用 2DE 和串联 MS 来鉴定药物在 A-T 细胞中而不是在健康细胞中影响的蛋白质。从总共 746±63 个中确定了 34 个蛋白质。通过微阵列进行转录组分析显示，599 个 A-T 和 362 个野生型（WT）基因的表达存在差异，并且蛋白质丰度与相应基因表达变化之间存在健康不匹配。蛋白质组学和转录组学谱允许对网络途径进行分析，以确定地塞米松在 Dexa 处理细胞中影响的生物学和分子功能。本综合研究提供了地塞米松在 A-T 细胞模型中的作用机制的证据，还提供了该药物在其他测试细胞系中的更广泛影响的证据。
