Butterfield L H, Merino A, Golub S H, Shau H
Division of Surgical Oncology, UCLA School of Medicine, Los Angeles, CA 90095-1782, USA.
Antioxid Redox Signal. 1999 Winter;1(4):385-402. doi: 10.1089/ars.1999.1.4-385.
In the past decade, a new family of highly conserved antioxidant enzymes, Peroxiredoxins (Prxs), have been discovered and defined. There are two major Prx subfamilies: one subfamily uses two conserved cysteines (2-Cys) and the other uses 1-Cys to scavenge reactive oxygen species (ROS). This review focuses on the four mammalian 2-Cys members (Prx I-IV) that utilize thioredoxin as the electron donor for antioxidation. The array of biological activities of these proteins suggests that they may be evolutionarily important for cell function. For example, Prxs are capable of protecting cells from ROS insult and regulating the signal transduction pathways that utilize c-Abl, caspases, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) to influence cell growth and apoptosis. Prxs are also essential for red blood cell (RBC) differentiation and are capable of inhibiting human immunodeficiency virus (HIV) infection and organ transplant rejection. Distribution patterns indicate that Prxs are highly expressed in the tissues and cells at risk for diseases related to ROS toxicity, such as Alzheimer's and Parkinson's diseases and atherosclerosis. This interesting correlation suggests that Prxs are protective against ROS toxicity, yet overwhelmed by oxidative stress in some cells. Prxs tend to form large aggregates at high concentrations, a feature that may interfere with their normal protective function or may even render them cytotoxic. Imbalance in the expression of subtypes can also potentially increase their susceptibility to oxidative stress. Understanding the function and biological role of Prxs may lead to important discoveries about the cellular dysfunction of ROS-related diseases ranging from atherosclerosis to cancer to neurodegenerative diseases.
在过去十年中，人们发现并定义了一个新的高度保守的抗氧化酶家族——过氧化物酶（Prxs）。Prxs主要有两个亚家族：一个亚家族利用两个保守的半胱氨酸（2-Cys），另一个利用一个半胱氨酸（1-Cys）来清除活性氧（ROS）。本综述聚焦于四个利用硫氧还蛋白作为抗氧化电子供体的哺乳动物2-Cys成员（Prx I-IV）。这些蛋白质的一系列生物活性表明，它们在细胞功能的进化过程中可能具有重要意义。例如，Prxs能够保护细胞免受ROS损伤，并调节利用c-Abl、半胱天冬酶、核因子-κB（NF-κB）和激活蛋白-1（AP-1）影响细胞生长和凋亡的信号转导通路。Prxs对于红细胞（RBC）分化也至关重要，并且能够抑制人类免疫缺陷病毒（HIV）感染和器官移植排斥反应。分布模式表明，Prxs在与ROS毒性相关疾病（如阿尔茨海默病、帕金森病和动脉粥样硬化）的风险组织和细胞中高度表达。这种有趣的相关性表明，Prxs可抵御ROS毒性，但在某些细胞中会被氧化应激 overwhelm。Prxs在高浓度时往往会形成大聚集体，这一特性可能会干扰它们的正常保护功能，甚至可能使其具有细胞毒性。亚型表达的失衡也可能会增加它们对氧化应激的易感性。了解Prxs的功能和生物学作用可能会在从动脉粥样硬化到癌症再到神经退行性疾病等与ROS相关疾病的细胞功能障碍方面带来重要发现。
