Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid β-peptides induced oxidative stress and reduces NF-κB activation
Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid β-peptides induced oxidative stress and reduces NF-κB activation
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DOI：
10.1016/s0197-0186(01)00136-x
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发表时间：
2002-07-01
影响因子：
4.2
通讯作者：
Schettini, G
中科院分区：
文献类型：
--
作者：
Bisaglia, M;Venezia, V;Schettini, G
目前的研究结果表明，非典型的非甾体抗炎药，如对乙酰氨基酚，保留了通过氧化应激损伤恢复淀粉样β肽驱动的神经元凋亡的能力。此外，这种化合物降低了NIF-kappaB结合活性的增加，这发生在这些退行性conditions.Therapeutic干预，旨在减少阿尔茨海默氏病（AD）的炎症反应，最近提出了非甾体抗炎药的应用。尽管对乙酰氨基酚的抗炎特性存在争议，但在淀粉样蛋白驱动的星形细胞瘤细胞变性模型中，对乙酰氨基酚被证明是有效的。在此基础上，我们分析了对乙酰氨基酚对不同A β肽对大鼠原代海马神经元和大鼠嗜铬细胞瘤细胞系的毒性的作用。我们发现，淀粉样蛋白β片段1-40和1-42诱导的线粒体氧化还原活性损伤对两种细胞培养物的保护作用一致，与凋亡核碎片的显着减少相关。的保护活性的抗氧化剂组分出现从分析的减少磷脂过氧化，也从一个显着减少的细胞质中积累的过氧化物在嗜铬细胞瘤细胞系。此外，激活的NF-κ B的淀粉样蛋白衍生肽大大受损对乙酰氨基酚预处理海马cells.This证据指出，抗氧化剂和抗转录特性的对乙酰氨基酚除了已知的能力，干扰炎症中枢神经系统内，并建议它可以被开发作为一种可能的治疗方法，对AD。(C)2002年由Elsevier Science Ltd.出版
The present findings show that an atypical non-steroidal anti-inflammatory drug, such as acetaminophen, retains the ability to recover amyloid beta-peptides driven neuronal apoptosis through the impairment of oxidative stress. Moreover, this compound reduces the increased NIF-kappaB binding activity, which occurs in these degenerative conditions.Therapeutic interventions aimed at reducing the inflammatory response in Alzheimer's disease (AD) recently suggested the application of non-steroidal anti-inflammatory drugs. Although the anti-inflammatory properties of acetaminophen are controversial, it emerged that in an amyloid-driven astrocytoma cell degeneration model acetaminophen proved to be effective.On these bases, we analyzed the role of acetaminophen against the toxicity exerted by different Abeta-peptides on rat primary hippocampal neurons and on a rat pheochromocytoma cell line. We found a consistent protection from amyloid beta-fragments 1-40 and 1-42-induced impairment of mitochondrial redox activity on both cell cultures, associated with a marked reduction of apoptotic nuclear fragmentation. An antioxidant component of the protective activity emerged from the analysis of the reduction of phospholipid peroxidation, and also from a significant reduction of cytoplasmic accumulation of peroxides in the pheochromocytoma cell line. Moreover, activation of NF-kappaB by amyloid-derived peptides was greatly impaired by acetaminophen pre-treatment in hippocampal cells.This evidence points out antioxidant and anti-transcriptional properties of acetaminophen besides the known capability to interfere with inflammation within the central nervous system, and suggests that it can be exploited as a possible therapeutic approach against AD. (C) 2002 Published by Elsevier Science Ltd.