Gender-related differences in the oxidant state of cells in Fanconi anemia heterozygotes
Gender-related differences in the oxidant state of cells in Fanconi anemia heterozygotes
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DOI：
10.1515/bc.2011.064
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发表时间：
2011-06-01
影响因子：
3.7
通讯作者：
Joksic, Gordana
中科院分区：
文献类型：
--
作者：
Petrovic, Sandra;Leskovac, Andreja;Joksic, Gordana
范可尼贫血（FA）是一种罕见的易患癌症的遗传性疾病，其特征是进行性骨髓衰竭、染色体不稳定和氧化还原异常。有许多生化和遗传数据，这强烈表明FA细胞经历增加的氧化应激。本研究旨在阐明对照、特发性骨髓衰竭（idBMF）和FA细胞之间是否存在氧化状态的差异，并分析FA杂合子携带者细胞的氧化状态。本研究的结果证实了FA细胞的体内促氧化状态，并清楚地表明FA患者可以根据细胞的氧化状态与idBMF患者区分开。FA突变的女性携带者也表现出体内促氧化状态的特征，表现出与FA患者相似的方式。另一方面，FA雄性携带者和idBMF家族中细胞的氧化状态与对照组相比没有显示出任何显著差异。我们表明，改变氧化状态的影响细胞凋亡的易感性在FA患者和女性运营商。这些结果强调了需要进一步研究线粒体遗传在FA发病机制中的可能作用。
Fanconi anemia (FA) is a rare cancer-prone genetic disorder characterized by progressive bone marrow failure, chromosomal instability and redox abnormalities. There is much biochemical and genetic data, which strongly suggest that FA cells experience increased oxidative stress. The present study was designed to elucidate if differences in oxidant state exist between control, idiopathic bone marrow failure (idBMF) and FA cells, and to analyze oxidant state of cells in FA heterozygous carriers as well. The results of the present study confirm an in vivo prooxidant state of FA cells and clearly indicate that FA patients can be distinguished from idBMF patients based on the oxidant state of cells. Female carriers of FA mutation also exhibited hallmarks of an in vivo prooxidant state behaving in a similar manner as FA patients. On the other hand, the oxidant state of cells in FA male carriers and idBMF families failed to show any significant difference vs. controls. We demonstrate that the altered oxidant state influences susceptibility of cells to apoptosis in both FA patients and female carriers. The results highlight the need for further research of the possible role of mitochondrial inheritance in the pathogenesis of FA.