Dickinson Bryan C, Tang Yan, Chang Zengyi, Chang Christopher J
Department of Chemistry, The University of California, Berkeley, CA 94720, USA.
Chem Biol. 2011 Aug 26;18(8):943-8. doi: 10.1016/j.chembiol.2011.07.005.
Hydrogen peroxide (H(2)O(2)) can serve as a beneficial signaling agent or toxin depending on its concentration and location within a cell or organism. Methods to measure the localized accumulation of H(2)O(2) in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H(2)O(2), Nuclear Peroxy Emerald 1 (NucPE1), to selectively interrogate ROS fluxes within this sensitive organelle. NucPE1 selectively accumulates in the nuclei of a variety of mammalian cell lines as well as in whole model organisms like Caenorhabditis elegans, where it can respond to subcellular changes in H(2)O(2) fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H(2)O(2) levels in worms overexpressing sir-2.1 compared with wild-type congeners, supporting a link between this longevity-promoting sirtuin protein and enhanced regulation of nuclear ROS pools.
过氧化氢(H₂O₂)可作为一种有益的信号分子或毒素,这取决于其在细胞或生物体中的浓度和位置。测量活样本中H₂O₂局部积累的方法仍然有限。为满足这一需求,我们开发了一种用于H₂O₂的核定位荧光探针——核过氧翡翠1(NucPE1),以选择性地检测这个敏感细胞器内的活性氧通量。NucPE1选择性地积累在多种哺乳动物细胞系的细胞核中,以及在整个模式生物如秀丽隐杆线虫中,在那里它可以对H₂O₂通量的亚细胞变化做出反应。此外,体内NucPE1成像显示,与野生型同类相比,过表达sir-2.1的蠕虫细胞核中H₂O₂水平降低,这支持了这种促进长寿的沉默调节蛋白与增强的核活性氧池调节之间的联系。