Ex vivo protective effects of nicotinamide and 3-aminobenzamide on rat synaptosomes treated with Aβ(1-42)
Ex vivo protective effects of nicotinamide and 3-aminobenzamide on rat synaptosomes treated with Aβ(1-42)
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DOI：
10.1002/cbf.3049
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发表时间：
2014-10-01
影响因子：
3.6
通讯作者：
Yalcin, Ayfer
中科院分区：
文献类型：
--
作者：
Bayrakdar, Ezgi Turunc;Armagan, Guliz;Yalcin, Ayfer
阿尔茨海默病（AD）是痴呆的最常见形式，其特征在于存在老年斑和神经元缠结，沿着突触丧失。AD的发病机制尚不清楚，但氧化应激和线粒体功能障碍是重要因素。聚（腺苷二磷酸核糖）聚合酶-1（PARP-1）的过度活化已被认为会导致神经退行性过程中的神经炎症和细胞死亡。本研究的目的是研究PARP-1抑制剂3-氨基苯甲酰胺（3-AB）和烟酰胺（NA）对淀粉样肽（1-42）（A（1- 42））诱导的氧化损伤和线粒体还原能力对分离的突触体的保护作用。大鼠腹腔注射3-AB（30- 100 mg·kg ~（-1））、NA（100- 500 mg·kg ~（-1））或生理盐水7 d。将突触体与10- 30 M A（1-42）或盐水在37 ℃下孵育6小时。离体A（1-42）处理显著诱导生理盐水组突触体的氧化应激和线粒体功能障碍，而3-AB和NA组突触体的脂质过氧化、活性氧产生和蛋白质氧化显著降低。此外，NA和3-AB都能够提高线粒体对A（1-42）的还原能力。这些数据表明，NA和3-AB可能具有保护作用，在神经退行性过程中，因为氧化应激水平的降低和线粒体功能的改善。版权所有（c）2014约翰威利父子有限公司
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles, along with synaptic loss. The underlying mechanisms of AD are not clarified yet, but oxidative stress and mitochondrial dysfunction are important factors. Overactivation of poly(adenosine diphosphate ribose) polymerase-1 (PARP-1) enzyme has been known to cause neuroinflammation and cell death in neurodegenerative processes. The aim of the present study was to investigate the protective effects of the PARP-1 inhibitors, 3-aminobenzamide (3-AB) and nicotinamide (NA), against amyloid peptide (1-42) (A(1-42))-induced oxidative damage and mitochondrial reduction capacity on isolated synaptosomes. Rats were injected intraperitoneally with 3-AB (30-100mgkg(-1)), NA (100-500mgkg(-1)) or with saline for 7days. Synaptosomes were incubated with 10-30M A(1-42) or saline for 6h at 37 degrees C. Ex vivo A(1-42) treatment significantly induced oxidative stress and mitochondrial dysfunction in synaptosomes of the saline group, while synaptosomes of 3-AB and NA groups showed significant decreases in lipid peroxidation, reactive oxygen species production and protein oxidation. Moreover, both NA and 3-AB were able to improve the mitochondrial reduction capacity against A(1-42). These data suggest that NA and 3-AB may have protective effects in neurodegenerative processes because of the reduced levels of oxidative stress and the improvement of mitochondrial function. Copyright (c) 2014 John Wiley & Sons, Ltd.