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阿尔茨海默病患者淋巴细胞中活性氧生成增强。

Enhanced ROS-generation in lymphocytes from Alzheimer's patients.

作者信息

Leutner S, Schindowski K, Frölich L, Maurer K, Kratzsch T, Eckert A, Müller W E

机构信息

Department of Pharmacology, Biocenter, J. W. Goethe University of Frankfurt, Marie-Curie-Str. 9, 60439 Frankfurt am Main, Germany.

出版信息

Pharmacopsychiatry. 2005 Nov;38(6):312-5. doi: 10.1055/s-2005-916186.

Abstract

INTRODUCTION

Reactive oxygen species (ROS) have been implicated in neurodegeneration and seem to be involved in the physiology and pathophysiology of several diseases, including normal aging and Alzheimer's disease (AD). Enhanced ROS production in aging or AD is not restricted to the brain, but can also been seen in several peripheral tissues. The objective of the present study was to evaluate whether the mechanisms involved in the generation of oxidative stress in normal senescence and Alzheimer's disease are identical or not.

METHODS

We analysed intracellular basal levels of ROS in lymphocytes from AD patients and healthy young and aged not-demented subjects as well as ROS levels following stimulation with d-ribose and staurosporine in all three groups. ROS levels were measured by flow cytometry using the intracellular fluorescence dye dihydrorhodamine123 (DHR123).

RESULTS

Our study shows that AD lymphocytes have increased basal levels of ROS, low susceptibility to ROS stimulation by 2-deoxy- D-ribose (dRib) and an increased response to staurosporine when compared with age-matched controls.

DISCUSSION

The data suggest that the defect(s) responsible for enhanced ROS production in AD may involve different or additional biological pathways than those involved in enhanced ROS generation during aging.

摘要

引言

活性氧(ROS)与神经退行性变有关,似乎参与了包括正常衰老和阿尔茨海默病(AD)在内的多种疾病的生理和病理生理过程。衰老或AD中ROS产生的增加不仅限于大脑,在一些外周组织中也可见到。本研究的目的是评估正常衰老和阿尔茨海默病中氧化应激产生所涉及的机制是否相同。

方法

我们分析了AD患者以及健康年轻和老年非痴呆受试者淋巴细胞内ROS的基础水平,以及三组中用D-核糖和星形孢菌素刺激后的ROS水平。使用细胞内荧光染料二氢罗丹明123(DHR123)通过流式细胞术测量ROS水平。

结果

我们的研究表明,与年龄匹配的对照组相比,AD淋巴细胞的ROS基础水平升高,对2-脱氧-D-核糖(dRib)刺激ROS的敏感性较低,而对星形孢菌素的反应增强。

讨论

数据表明,AD中ROS产生增加的原因可能涉及与衰老过程中ROS产生增加不同或额外的生物学途径。

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