Du Wei, Adam Zsuzsanna, Rani Reena, Zhang Xiaoling, Pang Qishen
Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Antioxid Redox Signal. 2008 Nov;10(11):1909-21. doi: 10.1089/ars.2008.2129.
Patients with the genomic instability syndrome Fanconi anemia (FA) commonly develop progressive bone marrow failure and have a high risk of cancer. The prominent role of the FA protein family involves DNA damage response and/or repair. Oxidative stress, defined as an imbalance between the production of reactive oxygen species and antioxidant defense, is considered to be an important pathogenic factor in leukemia-prone bone marrow diseases such as FA. Cellular responses inducing resistance to oxidative stress are important for cellular survival, organism lifespan, and cancer prevention, but until recently, mammalian factors regulating resistance to oxidative stress have not been well characterized. Significant evidence supports excessive apoptosis of hematopoietic stem/progenitor cells, induced by stresses, most significantly oxidative stress, as a critical factor in the pathogenesis of bone marrow failure and leukemia progression in FA. In this brief review, we discuss the functional link between FA proteins and oxidative DNA damage response/repair, with emphasis on the implication of oxidative stress in the pathophysiology and abnormal hematopoiesis in FA.
患有基因组不稳定综合征范可尼贫血（FA）的患者通常会出现进行性骨髓衰竭，且患癌风险很高。FA蛋白家族的主要作用涉及DNA损伤反应和/或修复。氧化应激被定义为活性氧生成与抗氧化防御之间的失衡，被认为是诸如FA等易患白血病的骨髓疾病中的一个重要致病因素。诱导对氧化应激产生抗性的细胞反应对于细胞存活、生物体寿命和癌症预防都很重要，但直到最近，调节对氧化应激抗性的哺乳动物因子尚未得到很好的表征。大量证据支持造血干/祖细胞因应激（最显著的是氧化应激）而过度凋亡，这是FA中骨髓衰竭和白血病进展发病机制中的一个关键因素。在这篇简短的综述中，我们讨论了FA蛋白与氧化性DNA损伤反应/修复之间的功能联系，重点是氧化应激在FA病理生理学和异常造血中的影响。
