Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease.
Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease.
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DOI：
10.1111/j.1582-4934.2008.00163.x
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发表时间：
2008-06
影响因子：
5.3
通讯作者：
Butterfield DA
中科院分区：
文献类型：
--
作者：
Cenini G;Sultana R;Memo M;Butterfield DA
氧化应激与阿尔茨海默病（Alzheimer's disease，AD）的发病机制有关。AD及其早期形式轻度认知功能障碍（MCI）都具有升高的脑膜氧化损伤。肿瘤抑制因子和转录因子p53在氧化应激引发的神经元凋亡中起关键作用。在包括AD在内的许多神经系统疾病中，细胞凋亡导致神经元死亡。在这项研究中，我们研究了p53的表达在大脑皮层的一个特定区域，即顶下小叶（IPL），在MCI和AD脑，以测试的假设，这种促凋亡蛋白的改变可能参与神经元死亡的进展AD。通过免疫沉淀试验，我们还调查了是否4-羟基-2-transnonenal（HNE），脂质过氧化反应的产物，结合过量的p53在IPL与MCI和AD的受试者相比，控制。总之，这些数据提供了证据表明，p53参与MCI和AD中的神经元死亡，表明观察到的改变是AD进展中的早期事件。此外，HNE可能是氧化应激诱导神经元凋亡的一种新的非蛋白质介质。
Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Both AD and arguably its earlier form, mild cognitive impairment (MCI), have elevated membrane oxidative damage in brain. The tumor suppressor and transcription factor p53 plays a pivotal function in neuronal apoptosis triggered by oxidative stress. Apoptosis contributes to neuronal death in many neurological disorders, including AD. In this study, we investigated p53 expression in a specific region of the cerebral cortex, namely the inferior parietal lobule (IPL), in MCI and AD brain, to test the hypothesis that alterations of this pro-apoptotic protein may be involved in neuronal death in the progression of AD. By immunoprecipitation assay, we also investigated whether 4-hydroxy-2-transnonenal (HNE), an aldehydic product of lipid peroxidation, was bound in excess to p53 in IPL from subjects with MCI and AD compared to control. Overall, the data provide evidence that p53 is involved in the neuronal death in both MCI and AD, suggesting that the observed alterations are early events in the progression of AD. In addition, HNE may be a novel non-protein mediator of oxidative stress-induced neuronal apoptosis.
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影响因子：
56.9
作者：
CHO, YJ;GORINA, S;PAVLETICH, NP
通讯作者：
PAVLETICH, NP
影响因子：
2.5
作者：
Butterfield, DA;Reed, T;Sultana, R
通讯作者：
Sultana, R
影响因子：
4.1
作者：
Ji, C;Amarnath, V;Marnett, LJ
通讯作者：
Marnett, LJ
DOI：
10.1006/bbrc.1997.6301
发表时间：
1997-03-17
影响因子：
3.1
作者：
Kitamura, Y;Shimohama, S;Taniguchi, T
通讯作者：
Taniguchi, T
DOI：
10.1073/pnas.062059899
发表时间：
2002-03-19
影响因子：
11.1
作者：
da Costa, CA;Paitel, E;Checler, F
通讯作者：
Checler, F