Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction

M. H. Tran, K. Yamada, A. Nakajima, M. Mizuno, J. He, H. Kamei, T. Nabeshima

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Amyloid β (Aβ) is a critical factor involved in the pathogenesis of Alzheimer's disease (AD). We have previously demonstrated that continuous intracerebroventricular infusion of Aβ1-40 induced a time-dependent expression of the inducible nitric oxide (NO) synthase (iNOS) and an overproduction of NO in the rat hippocampus. The pathophysiological significance of the overproduction of NO on brain function was manifested by an impairment of nicotine-evoked acetylcholine(ACh) release and memory deficits.4 Molecular mechanisms by which NO participates in the Aβ-induced brain dysfunction, however, remain to be determined. Here we show that chronic Aβ1-40 infusion caused a robust peroxynitrite formation and subsequent tyrosine nitration of proteins in the hippocampus. Immunoprecipitation and Western blot analyses further revealed that synaptophysin, a synaptic protein, was a main target of tyrosine nitration. Chronic infusion of Aβ1-40 resulted in an impairment of nicotine-evoked ACh release as analyzed by microdialysis. Daily treatment with the iNOS inhibitor aminoguanidine (AG) or the peroxynitrite scavenger uric acid (UA) prevented the tyrosine nitration of synaptophysin as well as the impairment of nicotine-evoked ACh release induced by Aβ. Our findings suggest that the tyrosine nitration of synaptophysin is related to Aβ-induced impairment of ACh release.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalMolecular Psychiatry
Volume8
Issue number4
DOIs
Publication statusPublished - 03-06-2003

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Synaptophysin
Amyloid
Cholinergic Agents
Acetylcholine
Tyrosine
Nicotine
Nitric Oxide
Peptides
Peroxynitrous Acid
Hippocampus
Proteins
Far-Western Blotting
Intraventricular Infusions
Microdialysis
Brain
Nitric Oxide Synthase Type II
Uric Acid
Immunoprecipitation
Alzheimer Disease
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Tran, M. H. ; Yamada, K. ; Nakajima, A. ; Mizuno, M. ; He, J. ; Kamei, H. ; Nabeshima, T. / Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction. In: Molecular Psychiatry. 2003 ; Vol. 8, No. 4. pp. 407-412.
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Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction. / Tran, M. H.; Yamada, K.; Nakajima, A.; Mizuno, M.; He, J.; Kamei, H.; Nabeshima, T.

In: Molecular Psychiatry, Vol. 8, No. 4, 03.06.2003, p. 407-412.

Research output: Contribution to journalArticle

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