title: Vitamin E inhibits oxidative stress-induced denaturation of nerve terminal proteins involved in neurotransmission.
abstract: One characteristic of age-related neurodegeneration is thought to be cognitive deficits caused by oxidative stress. Neurons in the brain are considered to be particularly vulnerable to oxidative stress, leading to neuronal oxidative damage and neurodegenerative disorders such as Alzheimer's disease (AD) and senile dementia. The process of fusing synaptic plasma membranes and synaptic vesicles involves particular proteins, such as the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins for docking both membranes, and is integral to neurotransmission. To elucidate whether oxidative stress induces denaturation of SNARE proteins, and whether vitamin E can counteract this process, changes in the expression of synaptobrevin, synaptotagmin, SNAP-25, and syntaxin-1 in rat brain nerve terminals were analyzed using an immunoblotting method. The results showed that oxidative stress induced significant reductions in the levels synaptobrevin and synaptotagmin in synaptic vesicles. Similarly, marked decreases in the levels of SNAP-25 and syntaxin-1 in pre-synaptic plasma membranes were also observed. In the absence of oxidative stress, vitamin E-deficient rats exhibited similar decreases in these proteins. In contrast, it was found that decreases in SNARE proteins, except for SNAP-25, were not observed in vitamin E-supplemented rats, even when the rats were subjected to oxidative stress. These results suggest that reactive oxygen species generated by oxidative stress are detrimental to neurons, resulting in the oxidation of SNARE proteins, thereby disrupting neurotransmission. Additionally, vitamin E is capable of protecting against such neurodegeneration.
authors.affiliation: Shibaura Institute of Technology, Division of Biochemistry, Minuma-ku, Saitama-city, Saitama, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kaneai
authors.forename: Masaya
authors.initials: M
authors.lastname: Arai
authors.forename: Hirokatsu
authors.initials: H
authors.lastname: Takatsu
authors.forename: Koji
authors.initials: K
authors.lastname: Fukui
authors.forename: Shiro
authors.initials: S
authors.lastname: Urano
mesh_terms: D000818:Animals; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011489:Protein Denaturation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D050600:SNARE Proteins; D014810:Vitamin E