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生物活化的萝卜硫苷在体外阿尔茨海默病模型中改善细胞存活、上调磷酸化AKT并调节参与DNA修复的基因:一项网络转录组学分析

Bioactivated Glucoraphanin Improves Cell Survival, Upregulating Phospho-AKT, and Modulates Genes Involved in DNA Repair in an In Vitro Alzheimer's Disease Model: A Network-Transcriptomic Analysis.

作者信息

Minuti Aurelio, Mazzon Emanuela, Iori Renato, Chiricosta Luigi, Artimagnella Osvaldo

机构信息

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.

Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" Chieti-Pescara, 66100 Chieti, Italy.

出版信息

Nutrients. 2024 Dec 5;16(23):4202. doi: 10.3390/nu16234202.

DOI:10.3390/nu16234202
PMID:39683594
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11644231/
Abstract

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, for which a definitive cure is still missing. Recently, natural compounds have been investigated for their possible neuroprotective role, including the bioactivated product of glucoraphanin (GRA), the sulforaphane (SFN), which is highly rich in cruciferous vegetables. It is known that SFN alleviates neuronal dysfunction, apoptosis, and oxidative stress in the brain. In the light of this evidence, the aim of this study was to investigate the molecular effects of SFN pre-treatment in differentiated SH-SY5Y neurons exposed to β-amyloid (Aβ).

METHODS

To this end, we first evaluated first cell viability via the Thiazolyl Blue Tetrazolium Bromide (MTT) assay, and then we analyzed the transcriptomic profiles by next-generation sequencing (NGS). Finally, we used a network analysis in order to understand which biological processes are affected, validating them by Western blot assay.

RESULTS

SFN pre-treatment counteracted Aβ-induced loss of cell viability. The network-transcriptomic analysis revealed that SFN upregulates genes associated with DNA repair, such as , , , , , , , , and Finally, SFN also increased the phosphorylation of AKT, which is associated with DNA repair and cell survival.

CONCLUSIONS

These data suggest that SFN is a natural compound that could be suitable in the prevention of AD, thanks to its neuroprotective role in increasing cell survival, potentially restoring DNA damage induced by Aβ exposure.

摘要

背景/目的:阿尔茨海默病(AD)是最常见的神经退行性疾病之一,目前仍缺乏确切的治愈方法。最近,人们对天然化合物的潜在神经保护作用进行了研究,其中包括富含十字花科蔬菜的萝卜硫苷(GRA)的生物活化产物萝卜硫素(SFN)。已知SFN可减轻大脑中的神经元功能障碍、细胞凋亡和氧化应激。鉴于此证据,本研究旨在探讨SFN预处理对暴露于β-淀粉样蛋白(Aβ)的分化SH-SY5Y神经元的分子影响。

方法

为此,我们首先通过噻唑蓝四唑溴盐(MTT)试验评估细胞活力,然后通过下一代测序(NGS)分析转录组谱。最后,我们进行网络分析以了解哪些生物过程受到影响,并通过蛋白质印迹分析进行验证。

结果

SFN预处理抵消了Aβ诱导的细胞活力丧失。网络转录组分析显示,SFN上调了与DNA修复相关的基因,如 、 、 、 、 、 、 、 和 。最后,SFN还增加了与DNA修复和细胞存活相关的AKT磷酸化。

结论

这些数据表明,SFN是一种天然化合物,由于其在提高细胞存活率方面的神经保护作用,可能有助于预防AD, potentially restoring DNA damage induced by Aβ exposure.(原文此处表述有误,正确翻译为:可能恢复由Aβ暴露引起的DNA损伤。)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/095005bdc1f5/nutrients-16-04202-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/04a961963d56/nutrients-16-04202-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/8ef4d7f2c1fa/nutrients-16-04202-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/0bd6e2e030b5/nutrients-16-04202-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/2b0b846ac148/nutrients-16-04202-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/36c5e5c203aa/nutrients-16-04202-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/72c939d0b012/nutrients-16-04202-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/095005bdc1f5/nutrients-16-04202-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/04a961963d56/nutrients-16-04202-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/2290f8fcc82d/nutrients-16-04202-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/8ef4d7f2c1fa/nutrients-16-04202-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/0bd6e2e030b5/nutrients-16-04202-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/2b0b846ac148/nutrients-16-04202-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/36c5e5c203aa/nutrients-16-04202-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/72c939d0b012/nutrients-16-04202-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b3/11644231/095005bdc1f5/nutrients-16-04202-g008.jpg

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