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

Tran, Manh Hung; Yamada, Kiyofumi; Nakajima, Akira; Mizuno, Makoto; He, Jue; Kamei, Hiroyuki; Nabeshima, Toshitaka

doi:10.1038/sj.mp.4001240

Cited by 65 publications

(52 citation statements)

References 29 publications

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“…It has been confirmed that peroxynitrite-mediated damage contributes to Aβ-induced neuronal toxicity and cognitive deficits 10,11 and is widespread in the brain of AD patients 12 . In AD patients, learning and memory are impaired by the concomitant loss of the cholinergic marker enzyme, choline acetyltransferase (ChAT), in the cerebralcortex 13 .…”

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confidence: 98%

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2016

IJPSR

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ABSTRACT:Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of isorhamnetin (IRN) against amyloid beta 25-35 (Aβ 25-35)-induced memory impairment and oxidative damage in rats. Memory task was assessed using Y-arm maze and it revealed the impairment in spatial memory. The IRN treated rats showed improvement in memory task. Aβ 25-35 induced animals also exhibited increase in hydrogen peroxide (H 2 O 2), Monoamine oxidase activity (MAO) and decrease in choline acetyltransferase (ChAT) activity. It also enhanced the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine, IL-β whereas all these abnormalities were reduced significantly in IRN treated rats showing the neuroprotective effect of IRN against Aβ 25-35 induced Alzheimer's disease (AD). Thus, IRN may be a potential therapeutic agent for Alzheimer's disease.

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confidence: 98%

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2016

IJPSR

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“…The reduction in synaptophysin expression may contribute to altered behavior in autism, since animals with a spatial learning deficit display a significant reduction in synaptophysin levels [69] . Synaptophysin has been shown to be the main target of nitration in the rat hippocampus following the infusion of amyloid beta-protein [70] . SOD is an endogenous scavenger of superoxide anions [71] .…”

Section: Heavy Metals/toxins (Hg) Free Radical Scavengers Dietary Antmentioning

confidence: 99%

Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

Sajdel-Sulkowska¹,

Lipiński²,

Windom³

et al. 2008

American J. of Biochemistry and Biotechnology

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It has been suggested that oxidative stress and/or mercury compounds play an important role in the pathophysiology of autism. This study compared for the first time the cerebellar levels of the oxidative stress marker 3-nitrotyrosine (3-NT), mercury (Hg) and the antioxidant selenium (Se) levels between control and autistic subjects. Tissue homogenates were prepared in the presence of protease inhibitors from the frozen cerebellar tissue of control (n=10; mean age, 15.5 years; mean PMI, 15.5 hours) and autistic (n=9; mean age 12.1 years; mean PMI, 19.3 hours) subjects. The concentration of cerebellar 3-NT, determined by ELISA, in controls ranged from 13.69 to 49.04 pmol g 1 of tissue; the concentration of 3-NT in autistic cases ranged from 3.91 to 333.03 pmol g 1 of tissue. Mean cerebellar 3-NT was elevated in autism by 68.9% and the increase was statistically significant (p=0.045). Cerebellar Hg, measured by atomic absorption spectrometry ranged from 0.9 to 35 pmol g 1 tissue in controls (n=10) and from 3.2 to 80.7 pmol g 1 tissue in autistic cases (n=9); the 68.2% increase in cerebellar Hg was not statistically significant. However, there was a positive correlation between cerebellar 3-NT and Hg levels (r=0.7961, p=0.0001). A small decrease in cerebellar Se levels in autism, measured by atomic absorption spectroscopy, was not statistically significant but was accompanied by a 42.9% reduction in the molar ratio of Se to Hg in the autistic cerebellum. While preliminary, the results of the present study add elevated oxidative stress markers in brain to the growing body of data reflecting greater oxidative stress in autism.

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“…A␤-induced expression of TNF-␣ leads to overexpression of inducible nitric-oxide synthase (iNOS) in experimental animals (Akama and Van Eldik, 2000;Combs et al, 2001;Alkam et al, 2008). Peroxynitrite (ONOO Ϫ ) is one of the products formed from nitric oxide and superoxide and has a variety of chemical reactions producing compounds such as nitrotyrosine (Reiter et al, 2000;Tran et al, 2003). Interestingly, the accumulation of nitrotyrosine correlated with increased levels of cerebral A␤ and the severity of cognitive impairment (Smith et al, 1997;Ishii et al, 2000;Tran et al, 2003).…”

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confidence: 99%

Silibinin Attenuates Amyloid β_25–35Peptide-Induced Memory Impairments: Implication of Inducible Nitric-Oxide Synthase and Tumor Necrosis Factor-α in Mice

Lu¹,

Mamiya²,

Lu³

et al. 2009

J Pharmacol Exp Ther

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In Alzheimer's disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Silibinin (silybin), a flavonoid derived from the herb milk thistle, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether silibinin improves amyloid ␤ (A␤) peptide-induced neurotoxicity. In this study, we examined the effect of silibinin on the fear-conditioning memory deficits, inflammatory response, and oxidative stress induced by the intracerebroventricular injection of A␤ peptide [25][26][27][28][29][30][31][32][33][34][35] (A␤ [25][26][27][28][29][30][31][32][33][34][35] ) in mice. Mice were treated with silibinin (2, 20, and 200 mg/kg p.o., once a day for 8 days) from the day of the A␤ 25-35 injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitrotyrosine levels in the hippocampus and amygdala were examined (day 8). The mRNA expression of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor-␣ (TNF-␣) in the hippocampus and amygdala was measured 2 h after the A␤ 25-35 injection. We found that silibinin significantly attenuated memory deficits caused by A␤ [25][26][27][28][29][30][31][32][33][34][35] in the cued and contextual fear-conditioning test. Silibinin significantly inhibited the increase in nitrotyrosine levels in the hippocampus and amygdala induced by A␤ [25][26][27][28][29][30][31][32][33][34][35] . Nitrotyrosine levels in these regions were negatively correlated with memory performance. Moreover, real-time RT-PCR revealed that silibinin inhibited the overexpression of iNOS and TNF-␣ mRNA in the hippocampus and amygdala induced by A␤ [25][26][27][28][29][30][31][32][33][34][35] . These findings suggest that silibinin (i) attenuates memory impairment through amelioration of oxidative stress and inflammatory response induced by A␤ [25][26][27][28][29][30][31][32][33][34][35] and (ii) may be a potential candidate for an AD medication.

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

Cited by 65 publications

References 29 publications

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Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

Silibinin Attenuates Amyloid β_25–35Peptide-Induced Memory Impairments: Implication of Inducible Nitric-Oxide Synthase and Tumor Necrosis Factor-α in Mice

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

Cited by 65 publications

References 29 publications

Untitled

Untitled

Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

Silibinin Attenuates Amyloid β25–35Peptide-Induced Memory Impairments: Implication of Inducible Nitric-Oxide Synthase and Tumor Necrosis Factor-α in Mice

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Silibinin Attenuates Amyloid β_25–35Peptide-Induced Memory Impairments: Implication of Inducible Nitric-Oxide Synthase and Tumor Necrosis Factor-α in Mice