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SNAP25 is a pre‐synaptic target for the depressant action of reactive oxygen species on transmitter release
Author(s) -
Giniatullin A. R.,
Darios F.,
Shakirzyanova A.,
Davletov B.,
Giniatullin R.
Publication year - 2006
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 - 10.1111/j.1471-4159.2006.03997.x
Subject(s) - snap25 , reactive oxygen species , neurotransmission , synaptic vesicle , oxidative stress , neuroscience , synapse , biology , acetylcholine , neurotoxin , microbiology and biotechnology , chemistry , biochemistry , biophysics , pharmacology , receptor , vesicle , membrane
Reactive oxygen species (ROS) participate in various physiological and pathological processes in the nervous system, but the specific pathways that mediate ROS signalling remain largely unknown. Using electrophysiological techniques and biochemical evaluation of isolated fusion proteins, we explored the sensitivity to standard oxidative stress of the entire synapse, the pre‐synaptic machinery and essential fusion proteins underlying transmitter exocytosis. Oxidative stress induced by H 2 O 2 plus Fe 2+ inhibited both evoked and spontaneous quantal release from frog or mouse motor nerve endings, while it left post‐synaptic sensitivity unchanged. The depressant effect of H 2 O 2 on acetylcholine release was pertussis toxin‐insensitive, ruling out G‐protein cascades. Experiments with ionomycin, a Ca 2+ ionophore, revealed that ROS directly impaired the function of releasing machinery. In line with this, SNAP25, one of three essential fusion proteins, showed a selectively high sensitivity to the oxidative signals. Several ROS scavengers enhanced evoked synaptic transmission, consistent with tonic inhibition by endogenous ROS. Our data suggest that ROS‐induced impairment of releasing machinery is mediated by SNAP25, which appears to be a pre‐synaptic ROS sensor. This mechanism of ROS signalling could have widespread implications in the nervous system and might contribute to the pathogenesis of neurodegenerative diseases.

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