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The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke.


ABSTRACT: Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke.

SUBMITTER: Wu LJ 

PROVIDER: S-EPMC3314139 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke.

Wu Long-Jun LJ   Wu Gongxiong G   Akhavan Sharif M Reza MR   Baker Amanda A   Jia Yonghui Y   Fahey Frederic H FH   Luo Hongbo R HR   Feener Edward P EP   Clapham David E DE  

Nature neuroscience 20120304 4


Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, e  ...[more]

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