Lindl Kathryn A, Jordan-Sciutto Kelly L
Robert Schattner Center, School of Dental Medicine, Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.
Methods Mol Biol. 2008;477:229-43. doi: 10.1007/978-1-60327-517-0_18.
As organisms designed to depend upon oxygen to sustain life, humans are necessarily and continually exposed to damaging oxidizing agents. As a vital protective measure, oxygen-dependent organisms have developed a highly evolutionarily conserved mechanism for preventing oxidative stress. NF-E2 (nuclear factor (erythroid-derived 2))-related factor-2 (Nrf2) is the primary regulator of this endogenous antioxidant response. Many diseases that plague human society, ranging from various cancers to neurodegenerative diseases, have oxidative stress as a component of their etiology, and thus, much disease research has focused on Nrf2, both as a potential point of biological failure and as a promising therapeutic target. As a transcription factor, Nrf2 is active only when it is nuclear, and is regulated largely by its subcellular distribution. Thus, Nrf2 protein levels and subcellular localization are both key pieces of information when studying the endogenous antioxidant response. Immunofluorescent analysis (IFA) of Nrf2 in human tissue is a particularly powerful tool in the study of Nrf2 in disease, because it allows examination of both of these regulatory mechanisms that modulate Nrf2 activity.
作为依赖氧气维持生命的生物体,人类不可避免且持续地暴露于具有破坏性的氧化剂中。作为一项至关重要的保护措施,依赖氧气的生物体已经进化出一种高度保守的机制来预防氧化应激。NF-E2(核因子(红系衍生2))相关因子2(Nrf2)是这种内源性抗氧化反应的主要调节因子。困扰人类社会的许多疾病,从各种癌症到神经退行性疾病,其病因都包含氧化应激成分,因此,许多疾病研究都聚焦于Nrf2,将其既视为生物学功能失效的潜在关键点,又看作一个有前景的治疗靶点。作为一种转录因子,Nrf2只有在细胞核内时才具有活性,并且很大程度上受其亚细胞分布的调控。因此,在研究内源性抗氧化反应时,Nrf2蛋白水平和亚细胞定位都是关键信息。对人体组织中的Nrf2进行免疫荧光分析(IFA)是研究疾病中Nrf2的一种特别强大的工具,因为它能够检测调节Nrf2活性的这两种调控机制。