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个体易感性对氧化应激、防御系统与帕金森病之间的强关联有重大影响。

Individual susceptibility has a major impact on strong association between oxidative stress, defence systems and Parkinson's disease.

作者信息

Karahalil Bensu, Miser Salihoğlu Ece, Elkama Aylin, Orhan Gürdal, Saygın Evrim, Yardim Akaydin Sevgi

机构信息

Faculty of Pharmacy, Toxicology Department, Gazi University, Ankara, Turkey.

Biochemistry Department, Faculty of Pharmacy, Gazi University, Ankara, Turkey.

出版信息

Basic Clin Pharmacol Toxicol. 2022 Jan;130(1):158-170. doi: 10.1111/bcpt.13659. Epub 2021 Nov 7.

Abstract

Oxidative stress plays an important role in the degeneration of dopaminergic neurons, which causes Parkinson's disease (PD). Oxidative stress products, antioxidant and their balance have important roles in the development of oxidative stress-based PD. The impact of reactive oxygen species (ROS) and defence systems can be altered by genetic polymorphisms, and thus the risk of PD may also be affected. We aimed to investigate the possible association of individual susceptibility with the development of oxidative stress-based PD. For this purpose, we measured serum levels of folic acid, homocysteine, Vitamin B6 and B12 that play roles in folate-dependent one-carbon pathway, oxidant or antioxidant enzymes (NADPH oxidase, MnSOD, GPX), 8-OHdG and repair enzymes (OGG1, XRCC1 and MTH1) by ELISA, and analysed related gene polymorphisms by PCR-RFLP. XRCC1, ROS, NADPH and folic acid levels were found to be statistically higher in patients than controls. XRCC1, MnSOD and GPX activities were increased. We observed higher levels of 8-OHdG in patients with MnSOD and XRCC1 mutant genotypes and higher XRCC1 levels in patients with NOX p22 fox mutant genotypes rather than controls. We suggest that routinely clinical validation of major oxidative stress-related biomarkers will be a good approach to manage detrimental effects of PD.

摘要

氧化应激在多巴胺能神经元变性中起重要作用,而多巴胺能神经元变性会导致帕金森病(PD)。氧化应激产物、抗氧化剂及其平衡在基于氧化应激的帕金森病发展过程中具有重要作用。活性氧(ROS)和防御系统的影响可能会因基因多态性而改变,因此帕金森病的风险也可能受到影响。我们旨在研究个体易感性与基于氧化应激的帕金森病发展之间的可能关联。为此,我们通过酶联免疫吸附测定(ELISA)测量了在叶酸依赖性一碳途径中起作用的血清叶酸、同型半胱氨酸、维生素B6和B12水平、氧化酶或抗氧化酶(NADPH氧化酶、锰超氧化物歧化酶、谷胱甘肽过氧化物酶)、8-羟基脱氧鸟苷(8-OHdG)和修复酶(OGG1、XRCC1和MTH1),并通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)分析相关基因多态性。发现患者的XRCC1、ROS、NADPH和叶酸水平在统计学上高于对照组。XRCC1、锰超氧化物歧化酶和谷胱甘肽过氧化物酶的活性增加。我们观察到,锰超氧化物歧化酶和XRCC1突变基因型患者的8-OHdG水平较高,而NOX p22 fox突变基因型患者的XRCC1水平高于对照组。我们建议,对主要氧化应激相关生物标志物进行常规临床验证将是应对帕金森病有害影响的一个好方法。

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