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藻蓝胆素对SH-SY5Y细胞中谷氨酸诱导的兴奋性毒性以及多发性硬化症和脑缺血动物模型中基因表达的积极作用。

Positive effects of Phycocyanobilin on gene expression in glutamate-induced excitotoxicity in SH-SY5Y cells and animal models of multiple sclerosis and cerebral ischemia.

作者信息

Gardón Daniel Palenzuela, Cervantes-Llanos Majel, Matamoros Beatriz Piniella, Rodríguez Hanlet Camacho, Tan Chan-Yuan, Marín-Prida Javier, Falcón-Cama Viviana, Pavón-Fuentes Nancy, Lemus Jessica Gómez, Ruiz Laura de la Caridad Bakos, Argudin Tamara Díaz, Donato Gillian Martínez, Perera Yasser, Yang Ke, Pentón-Rol Giselle

机构信息

Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, Havana, PO Box 6162, Cuba.

China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology Co., Ltd, Yangjiaqiao Street, Lengshuitan District, Yongzhou City 425000, Hunan Province, China.

出版信息

Heliyon. 2022 Jun 20;8(6):e09769. doi: 10.1016/j.heliyon.2022.e09769. eCollection 2022 Jun.

Abstract

BACKGROUND

Oxidative stress has a predominant role in the pathogenesis of neurodegenerative diseases and therefore the modulation of genes and the identification of biological pathways associated with antioxidant therapies, have an impact on its treatment.

OBJECTIVE

The objective of this study was the comparison of 2 methods for the analysis of real-time PCR (qPCR) data, through the use of the evaluation of genes that mediate the effect of Phycocyanobilin (PCB) and its validation in animal models.

METHODS

We evaluated the effect of PCB:" in vitro" on gene modulation through qPCR analyzed by parametric ANOVA and multivariate principal component analysis (PCA) in a model of glutamate-induced excitotoxicity in the SH-SY5Y cell line and" in vivo"; in animal models of multiple sclerosis (MS) and cerebral ischemia (CI).

RESULTS

The results showed that PCA is a robust and powerful method that allows the assessment of gene expression profiles. We detected the significant down-regulation of the (NOX2), and HMOX1 by the action of PCB in SH-5YSH cell line insulted with Glutamate. The decrease in pro-inflammatory cytokines and markers related to apoptosis and innate immune response, mediated the effect of PCB in the animal models of MS and CI, respectively.

CONCLUSION

We concluded that the mechanisms by which PCB protected cells included the reduction of oxidative stress damage, which could contribute to its clinical efficacy for the treatment of neurodegenerative diseases.

摘要

背景

氧化应激在神经退行性疾病的发病机制中起主要作用,因此,与抗氧化疗法相关的基因调控和生物途径的鉴定对其治疗有影响。

目的

本研究的目的是通过评估介导藻蓝胆素(PCB)作用的基因并在动物模型中进行验证,比较两种实时定量聚合酶链反应(qPCR)数据分析方法。

方法

我们在SH-SY5Y细胞系谷氨酸诱导的兴奋性毒性模型中,通过参数方差分析和多变量主成分分析(PCA)对qPCR分析的PCB“体外”基因调控作用进行评估,并在多发性硬化症(MS)和脑缺血(CI)动物模型中进行“体内”评估。

结果

结果表明,PCA是一种强大且稳健的方法,可用于评估基因表达谱。在用谷氨酸损伤的SH-5YSH细胞系中,我们检测到PCB作用下烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)和血红素加氧酶1(HMOX1)显著下调。促炎细胞因子以及与细胞凋亡和先天免疫反应相关的标志物的减少,分别介导了PCB在MS和CI动物模型中的作用。

结论

我们得出结论,PCB保护细胞的机制包括减少氧化应激损伤,这可能有助于其治疗神经退行性疾病的临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/561e/9253351/e44faba463c1/gr1.jpg

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