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Caliphruria subedentata (Amaryllidaceae) decreases genotoxicity and cell death induced by β-amyloid peptide in SH-SY5Y cell line.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 2.3 ) Pub Date : 2018-11-18 , DOI: 10.1016/j.mrgentox.2018.06.010
Willian Orlando Castillo 1 , Andres Felipe Aristizabal-Pachon 2 , Elsa Sakamoto-Hojo 3 , Cristian Aldemar Gasca 4 , Fabio Antonio Cabezas-Fajardo 5 , Catarina Takahashi 3
Affiliation  

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuritic plaques (NPs), and neurofibrillary tangles (NFTs). β-Amyloid peptide 1-4 2 (Aβ(1-42)) is the principal component of NPs and is associated with oxidative stress, as well as dysfunction of cholinergic neurotransmission system and cell death. Nevertheless, one of the most promising therapeutic approaches for patients with AD is based on the pharmacological intervention to increases acetylcholine levels and reduces oxidative stress in AD brain. Previous studies have indicated that alkaloids from Amaryllidaceae family exhibit a wide range of biological activities. The purpose of this study was to investigate whether C. subedentata extract may modulate Aβ(1-42)- induced genotoxicity in SH-SY5Y cell line. Here, we conducted a set of bioassays to measure: viability, clonogenic survival, cell death, chromosome damage and DNA strand breaks. The results showed that Aβ(1-42) significantly inhibited cell viability through necrosis rather than apoptosis, increased the percentage of DNA damage and caused mitochondrial morphological alterations. Treatment with the C. subedentata extract led to a significant recovery of cell survival, decreased necrotic cell death and exerted an induction of antigenotoxic effects; additionally, the extract caigused inhibition of acetylcholinesterase (AChE). The present study confirms neuroprotective activities of C. subedentata belonging Amaryllidaceae family and provide a novel information to clarify the mechanisms by which the extracts decrease DNA damage levels induced by Aβ(1-42).

中文翻译:

圆柏(Amaryllidaceae)降低了SH-SY5Y细胞系中β-淀粉样肽诱导的遗传毒性和细胞死亡。

阿尔茨海默氏病(AD)是一种神经退行性疾病,其特征在于神经斑块(NPs)和神经原纤维缠结(NFTs)。β-淀粉样蛋白肽1-4 2(Aβ(1-42))是NP的主要成分,与氧化应激,胆碱能神经传递系统功能障碍和细胞死亡有关。然而,针对AD患者的最有希望的治疗方法之一是基于药理学干预以增加乙酰胆碱水平并降低AD脑中的氧化应激。先前的研究表明,金莲花科的生物碱具有广泛的生物活性。这项研究的目的是调查C. subedentata提取物是否可以调节Aβ(1-42)诱导的SH-SY5Y细胞系的遗传毒性。在这里,我们进行了一系列生物测定以衡量:生存力,无性系存活,细胞死亡,染色体损伤和DNA链断裂。结果表明,Aβ(1-42)通过坏死而不是凋亡显着抑制细胞活力,增加DNA损伤的百分比并引起线粒体形态改变。用C. subedentata提取物处理可显着恢复细胞存活率,减少坏死细胞死亡并诱导抗原毒性作用。此外,提取物对乙酰胆碱酯酶(AChE)产生抑制作用。本研究证实了隶属于丁香科的肉食梭菌的神经保护活性,并提供了新的信息来阐明提取物降低由Aβ(1-42)诱导的DNA损伤水平的机制。结果表明,Aβ(1-42)通过坏死而不是凋亡显着抑制细胞活力,增加DNA损伤的百分比并引起线粒体形态改变。用C. subedentata提取物处理可显着恢复细胞存活率,减少坏死细胞死亡并诱导抗原毒性作用。此外,提取物对乙酰胆碱酯酶(AChE)具有抑制作用。本研究证实了隶属于丁香科的肉食梭菌的神经保护活性,并提供了新的信息来阐明提取物降低由Aβ(1-42)诱导的DNA损伤水平的机制。结果表明,Aβ(1-42)通过坏死而不是凋亡显着抑制细胞活力,增加DNA损伤的百分比并引起线粒体形态改变。用C. subedentata提取物处理可显着恢复细胞存活率,减少坏死细胞死亡并诱导抗原毒性作用。此外,提取物对乙酰胆碱酯酶(AChE)产生抑制作用。本研究证实了隶属于丁香科的肉食梭菌的神经保护活性,并提供了新的信息来阐明提取物降低由Aβ(1-42)诱导的DNA损伤水平的机制。用C. subedentata提取物处理可显着恢复细胞存活率,减少坏死细胞死亡并诱导抗原毒性作用。此外,提取物对乙酰胆碱酯酶(AChE)产生抑制作用。本研究证实了隶属于丁香科的肉食梭菌的神经保护活性,并提供了新的信息来阐明提取物降低由Aβ(1-42)诱导的DNA损伤水平的机制。用C. subedentata提取物处理可显着恢复细胞存活率,减少坏死细胞死亡并诱导抗原毒性作用。此外,提取物对乙酰胆碱酯酶(AChE)产生抑制作用。本研究证实了隶属于丁香科的肉食梭菌的神经保护活性,并提供了新的信息来阐明提取物降低由Aβ(1-42)诱导的DNA损伤水平的机制。
更新日期:2019-11-01
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