A Nuclear-Localized Fluorescent Hydrogen Peroxide Probe for Monitoring Sirtuin-Mediated Oxidative Stress Responses In Vivo

被引:114
作者
Dickinson, Bryan C. [1 ]
Tang, Yan [3 ,4 ,5 ]
Chang, Zengyi [3 ,4 ,5 ]
Chang, Christopher J. [1 ,2 ]
机构
[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[3] Peking Univ, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China
[4] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China
[5] Peking Univ, Ctr Prot Sci, Beijing 100871, Peoples R China
来源
CHEMISTRY & BIOLOGY | 2011年 / 18卷 / 08期
关键词
LIVING CELLS; MAMMALIAN-CELLS; CHEMISTRY; BIOLOGY; PHOSPHORYLATION; INACTIVATION; MITOCHONDRIA; GENERATION; OXIDASE; H2O2;
D O I
10.1016/j.chembiol.2011.07.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hydrogen peroxide (H2O2) 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 H2O2 in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H2O2, 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 H2O2 fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H2O2 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.
引用
收藏
页码:943 / 948
页数:6
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