Van Wijk Roeland, Van Wijk Eduard P A, Wiegant Fred A C, Ives John
International Institute of Biophysics, Neuss, Germany.
Indian J Exp Biol. 2008 May;46(5):273-309.
Convincing evidence supports a role for oxidative stress in the pathogenesis of many chronic diseases. The model includes the formation of radical oxygen species (ROS) and the misassembly and aggregation of proteins when three tiers of cellular defence are insufficient: (a) direct antioxidative systems, (b) molecular damage repairing systems, and (c) compensatory chaperone synthesis. The aim of the present overview is to introduce (a) the basics of free radical and antioxidant metabolism, (b) the role of the protein quality control system in protecting cells from free radical damage and its relation to chronic diseases, (c) the basics of the ultraweak luminescence as marker of the oxidant status of biological systems, and (d) the research in human photon emission as a non-invasive marker of oxidant status in relation to chronic diseases. In considering the role of free radicals in disease, both their generation and their control by the antioxidant system are part of the story. Excessive free radical production leads to the production of heat shock proteins and chaperone proteins as a second line of protection against damage. Chaperones at the molecular level facilitate stress regulation vis-à-vis protein quali y control mechanisms. The manifestation of misfolded proteins and aggregates is a hallmark of a range of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amylotrophic lateral sclerosis, polyglutamine (polyQ) diseases, diabetes and many others. Each of these disorders exhibits aging-dependent onset and a progressive, usually fatal clinical course. The second part reviews the current status of human photon emission techniques and protocols for recording the human oxidative status. Sensitive photomultiplier tubes may provide a tool for non-invasive and continuous monitoring of oxidative metabolism. In that respect, recording ultraweak luminescence has been favored compared to other indirect assays. Several biological models have been used to illustrate the technique in cell cultures and organs in vivo. This initiated practical applications addressing specific human pathological issues. Systematic studies on human emission have presented information on: (a) procedures for reliable measurements, and spectral analysis, (b) anatomic intensity of emission and left-right symmetries, (c) biological rhythms in emission, (d) physical and psychological influences on emission, (e) novel physical characteristics of emission, and (f) the identification of ultraweak photon emission with the staging of ROS-related damage and disease. It is concluded that both patterns and physical properties of ultraweak photon emission hold considerable promise as measure for the oxidative status.
确凿的证据支持氧化应激在许多慢性疾病发病机制中的作用。该模型包括当细胞防御的三个层面不足时,活性氧(ROS)的形成以及蛋白质的错误组装和聚集:(a)直接抗氧化系统,(b)分子损伤修复系统,以及(c)代偿性伴侣蛋白合成。本综述的目的是介绍:(a)自由基和抗氧化剂代谢的基础知识,(b)蛋白质质量控制系统在保护细胞免受自由基损伤中的作用及其与慢性疾病的关系,(c)作为生物系统氧化状态标志物的超微弱发光的基础知识,以及(d)关于人类光子发射作为与慢性疾病相关的氧化状态非侵入性标志物的研究。在考虑自由基在疾病中的作用时,它们的产生以及抗氧化系统对其的控制都是其中的一部分。过量的自由基产生会导致热休克蛋白和伴侣蛋白的产生,作为防止损伤的第二道防线。分子水平上的伴侣蛋白通过蛋白质质量控制机制促进应激调节。错误折叠的蛋白质和聚集体的表现是一系列神经退行性疾病的标志,包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、多聚谷氨酰胺(polyQ)疾病、糖尿病等许多疾病。这些疾病中的每一种都表现出与年龄相关的发病以及渐进性的、通常是致命的临床病程。第二部分回顾了人类光子发射技术的现状以及记录人类氧化状态的方案。灵敏的光电倍增管可能为氧化代谢的非侵入性和连续监测提供一种工具。在这方面,与其他间接检测方法相比,记录超微弱发光更受青睐。已经使用了几种生物学模型来在细胞培养和体内器官中说明该技术。这引发了针对特定人类病理问题的实际应用。关于人类发射的系统研究提供了以下方面的信息:(a)可靠测量和光谱分析的程序,(b)发射的解剖强度和左右对称性,(c)发射中的生物节律,(d)对发射的物理和心理影响,(e)发射的新物理特性,以及(f)将超微弱光子发射与ROS相关损伤和疾病的分期进行识别。得出的结论是,超微弱光子发射的模式和物理特性作为氧化状态的测量方法都具有很大的前景。