A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo

Bryan C. Dickinson; Yan Tang; Zengyi Chang; Christopher J. Chang

doi:10.1016/j.chembiol.2011.07.005

A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo

Bryan C. Dickinson, Yan Tang, Zengyi Chang, Christopher J. Chang

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

Hydrogen peroxide (H ₂O 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 ₂O ₂ in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H ₂O 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 ₂O ₂ fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H ₂O 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.

Original language	English (US)
Pages (from-to)	943-948
Number of pages	6
Journal	Chemistry and Biology
Volume	18
Issue number	8
DOIs	https://doi.org/10.1016/j.chembiol.2011.07.005
State	Published - Aug 26 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2011.07.005

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title = "A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo",

abstract = "Hydrogen peroxide (H 2O 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 2O 2 in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H 2O 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 2O 2 fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H 2O 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.",

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AU - Dickinson, Bryan C.

AU - Tang, Yan

AU - Chang, Zengyi

AU - Chang, Christopher J.

PY - 2011/8/26

Y1 - 2011/8/26

N2 - Hydrogen peroxide (H 2O 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 2O 2 in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H 2O 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 2O 2 fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H 2O 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.

AB - Hydrogen peroxide (H 2O 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 2O 2 in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H 2O 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 2O 2 fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H 2O 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.

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A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo

Abstract

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