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Hydrogen Peroxide Inhibits the Vacuolar H + ‐ATPase in Brain Synaptic Vesicles at Micromolar Concentrations
Author(s) -
Wang Yalin,
Floor Erik
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020646.x
Subject(s) - synaptic vesicle , vesicle , dithiothreitol , chemistry , atpase , biochemistry , glutamate receptor , neurotransmitter , biophysics , glutathione , gtp' , microbiology and biotechnology , biology , enzyme , membrane , receptor
Hydrogen peroxide (H 2 O 2 ) is produced from several sources in brain and may be involved in neurodegeneration and second messenger signaling. Little is known about the effects of H 2 O 2 on transmitter storage in brain synaptic vesicles. Neurotransmitter uptake into synaptic vesicles is driven by an electrochemical proton gradient generated by the vacuolar H + ‐ATPase (V‐ATPase) in the vesicle membrane. We report here that the V‐ATPase in bovine brain synaptic vesicles is highly sensitive to inhibition by micromolar concentrations of H 2 O 2 . Glutamate uptake by the vesicles is also inhibited, very likely as a secondary consequence of ATPase inactivation. Dithiothreitol or reduced glutathione reverse H 2 O 2 ‐induced inhibition of the V‐ATPase, and ATP or GTP partially protect the ATPase from inhibition by H 2 O 2 . These and other results suggest that the mechanism of inhibition of the V‐ATPase by H 2 O 2 involves oxidation of a reactive cysteine sulfhydryl group in the ATP binding site. Inhibition of V‐ATPase activity would decrease the amount of transmitter stored in synaptic vesicles and thus down‐regulate transmitter release during episodes of oxidative stress or in response to second messenger signaling.