Extracellular redox state: Refining the definition of oxidative stress in aging
Extracellular redox state: Refining the definition of oxidative stress in aging
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DOI：
10.1089/rej.2006.9.169
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发表时间：
2006-06-01
影响因子：
2.6
通讯作者：
Jones, Dean P.
中科院分区：
文献类型：
--
作者：
Jones, Dean P.
衰老中的氧化应激可能是由于促氧化剂和抗氧化剂与过量的破坏性自由基化学的不平衡造成的。硫醇系统在控制这些过程中非常重要，既可以保护免受损害，又可以在氧化还原信号机制中感知危险并修复损害。许多研究小组与埃默里临床生物标志物实验室合作进行的研究表明，中心组织抗氧化剂谷胱甘肽（GSH）的氧化还原状态可以在人体血浆中测量，并提供了氧化应激的定量全身指标。人的血浆GSH/GSSG氧化还原反应随着年龄的增长、对化疗的反应、吸烟的结果以及与常见的年龄相关疾病（例如，2型糖尿病、心血管疾病）。然而，GSH/GSSG的氧化还原是不平衡的较大的血浆半胱氨酸/胱氨酸（Cys/CySS）池，和Cys/CySS的氧化还原随年龄变化的模式，是不同于GSH/GSSG的氧化还原。此外，体外研究表明，Cys/CySS氧化还原在体内发现的范围内的变化会影响信号通路，从而控制细胞增殖和氧化剂诱导的细胞凋亡。结果表明，当硫醇/二硫化物氧化还原状态被氧化时，自由基清除抗氧化剂的重要性增加。由于硫醇/二硫化物氧化还原状态本身在氧化还原信号传导和控制以及抗氧化保护中起作用，因此GSH/GSSG和Cys/CySS氧化还原状态可能提供中心参数以将环境影响和与衰老相关的变化进展联系起来。
Oxidative stress in aging can result from an imbalance of prooxidants and antioxidants with excessive, destructive free radical chemistry. Thiol systems are important in the control of these processes, both by protecting against damage and serving in redox signaling mechanisms to sense danger and repair the damage. Studies by a number of research groups in collaboration with the Emory Clinical Biomarkers Laboratory show that the redox state of the central tissue antioxidant, glutathione (GSH), can be measured in human plasma and provides a quantitative systemic indicator of oxidative stress. Plasma GSH/GSSG redox in humans becomes oxidized with age, in response to chemotherapy, as a consequence of cigarette smoking, and in association with common age-related diseases (e.g., type 2 diabetes, cardiovascular disease). However, the GSH/GSSG redox is not equilibrated with the larger plasma cysteine/cystine (Cys/CySS) pool, and the Cys/CySS redox varies with age in a pattern that is distinct from that of GSH/GSSG redox. Furthermore, in vitro studies show that variation in Cys/CySS redox over the range found in vivo affects signaling pathways, which control cell proliferation and oxidant-induced apoptosis. The results point to the conclusion that free radical scavenging antioxidants are of increased importance when thiol/disulfide redox states are oxidized. Because thiol/disulfide redox states, per se, function in redox signaling and control as well as antioxidant protection, GSH/GSSG and Cys/CySS redox states may provide central parameters to link environmental influences and progression of changes associated with aging.