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

Long-Jun Wu, Gongxiong Wu, M. Reza Akhavan Sharif, Amanda Baker, Yonghui Jia, Frederic H. Fahey, Hongbo R. Luo, Edward P. Feener, David E. Clapham

Research output: Contribution to journalArticle

117 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)565-573
Number of pages9
JournalNature neuroscience
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2012

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NADPH Oxidase
Protons
Stroke
Brain
Reactive Oxygen Species
Microglia
Brain Death
Phagocytes
Innate Immunity
Astrocytes
Ischemia
Electrons
Neurons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Wu, L-J., Wu, G., Sharif, M. R. A., Baker, A., Jia, Y., Fahey, F. H., ... Clapham, D. E. (2012). The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. Nature neuroscience, 15(4), 565-573. https://doi.org/10.1038/nn.3059
Wu, Long-Jun ; Wu, Gongxiong ; Sharif, M. Reza Akhavan ; Baker, Amanda ; Jia, Yonghui ; Fahey, Frederic H. ; Luo, Hongbo R. ; Feener, Edward P. ; Clapham, David E. / The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. In: Nature neuroscience. 2012 ; Vol. 15, No. 4. pp. 565-573.
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Wu, L-J, Wu, G, Sharif, MRA, Baker, A, Jia, Y, Fahey, FH, Luo, HR, Feener, EP & Clapham, DE 2012, 'The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke', Nature neuroscience, vol. 15, no. 4, pp. 565-573. https://doi.org/10.1038/nn.3059

The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. / Wu, Long-Jun; Wu, Gongxiong; Sharif, M. Reza Akhavan; Baker, Amanda; Jia, Yonghui; Fahey, Frederic H.; Luo, Hongbo R.; Feener, Edward P.; Clapham, David E.

In: Nature neuroscience, Vol. 15, No. 4, 01.04.2012, p. 565-573.

Research output: Contribution to journalArticle

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