摘要
生物体内大量的和毁灭性的自由基化学作用导致氧化和抗氧化的失衡,可造成与衰老相关的氧化应激。硫醇系统在这些生命过程中起重要的调控作用。它不仅能保护机体免受损伤,而且能通过氧化还原信号机制感知危险和修复损伤。研究发现,可对人体血浆中的谷胱甘肽(GSH)、半胱氨酸(Cys)等抗氧化剂的氧化还原状态(redoxstate,RS)进行检测,从而为氧化应激系统地提供定量指标。在细胞水平上,细胞调控胞外RS,胞内还原型谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)的RS随衰老向氧化方向偏移。对一些吸烟,化疗人群,以及患有与衰老相关的疾病(如2型糖尿病、心血管疾病)的受试者的研究表明,人体血浆中GSH/GSSG的RS随着年龄的增长而被不断氧化。然而,深入研究发现,GSH/GSSG的RS与其它主要的硫醇/二硫化物氧化还原对(Cys/CySS;硫氧还蛋白,Trx-1)的RS不守恒。此外,体内测得的氧还电位在一定范围内可影响细胞信号通路,并在体外能够调控细胞增殖与细胞凋亡。由于硫醇/二硫化物的RS具有指示细胞调控信号和氧化还原状态的作用,因此GSH/GSSG和Cys/CySS的RS仍然可以用作关联环境影响因子与衰老发展进程的重要参数。
Oxidative stress is often a result of an imbalance of pooxidants and antioxidants with excessive and destructive chemis- try of free radicals during aging. Thiol - related chemicals in biological system play an important role in the control of these processes. They protect not only against oxidative damages but also serve in redox signaling process to sense danger and repair the damages. A number of studies show that the redox state (RS) of antioxidants, such as glutathione (GSH) and cysteine (Cys), can be measured in tissue and plasma, which provides a quantitative index of oxidative stress. Studies on the patients with type - 2 diabetes and cardio- vascular diseases show that plasma RS of GSH/GSSG in humans becomes oxidized with age. However the GSH/GSSG redox is not e- quilibrated with other major thiol/disulfide couples ( Cys/CySS, Thiolredoxin, Trx - 1 ). Furthermore many studies show that varia- tion in redox potential in vivo over certain range may affect signaling pathways and control cell proliferation and oxidant - induced apoptosis in vitro. Because the RS of thiol/disulfide can indicate cellular control signals RS of GSH/GSSG and Cys/CySS redox states may still be used as the important parameters to link environmental influences and progression of changes associated with aging process.
出处
《国际老年医学杂志》
2011年第1期13-20,共8页
International Journal of Geriatrics
基金
国家高技术研究发展计划(2008AA022411)