Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Antioxid Redox Signal. 2011 Mar 15;14(6):1023-37. doi: 10.1089/ars.2010.3203. Epub 2010 Oct 28.
Accumulation of reactive oxygen species has been implicated in various diseases and aging. However, the precise physiological effects of accumulating oxidants are still largely undefined. Here, we applied a short-term peroxide stress treatment to young Caenorhabditis elegans and measured behavioral, physiological, and cellular consequences. We discovered that exposure to peroxide stress causes a number of immediate changes, including loss in mobility, decreased growth rate, and decreased cellular adenosine triphosphate levels. Many of these alterations, which are highly reminiscent of changes in aging animals, are reversible, suggesting the presence of effective antioxidant systems in young C. elegans. One of these antioxidant systems involves the highly abundant protein peroxiredoxin 2 (PRDX-2), whose gene deletion causes phenotypes symptomatic of chronic peroxide stress and shortens lifespan. Applying the quantitative redox proteomic technique OxICAT to oxidatively stressed wild-type and prdx-2 deletion worms, we identified oxidation-sensitive cysteines in 40 different proteins, including proteins involved in mobility and feeding (e.g., MYO-2 and LET-75), protein translation and homeostasis (e.g., elongation factor 1 [EFT-1] and heat shock protein 1), and adenosine triphosphate regeneration (e.g., nucleoside diphosphate kinase). The oxidative modification of some of these redox-sensitive cysteines may contribute to the physiological and behavioral changes observed in oxidatively stressed animals.
活性氧物质的积累与多种疾病和衰老有关。然而，积累氧化剂的确切生理影响在很大程度上仍未得到明确。在这里，我们对年轻的秀丽隐杆线虫应用了短期过氧化物应激处理，并测量了行为、生理和细胞后果。我们发现，暴露于过氧化物应激会引起许多立即发生的变化，包括运动能力丧失、生长速度下降和细胞三磷酸腺苷水平下降。这些改变中的许多与衰老动物中的改变非常相似，是可逆的，这表明年轻秀丽隐杆线虫中存在有效的抗氧化系统。其中一种抗氧化系统涉及高度丰富的蛋白质过氧化物还原酶 2（PRDX-2），其基因缺失会导致类似于慢性过氧化物应激的表型，并缩短寿命。我们应用定量氧化还原蛋白质组学技术 OxICAT 对氧化应激的野生型和 prdx-2 缺失线虫进行分析，鉴定出 40 种不同蛋白质中的氧化敏感半胱氨酸，这些蛋白质涉及运动和摄食（例如肌球蛋白-2 和 LET-75）、蛋白质翻译和稳态（例如延伸因子 1 [EFT-1]和热休克蛋白 1）以及三磷酸腺苷再生（例如核苷二磷酸激酶）。这些氧化敏感半胱氨酸中的一些的氧化修饰可能有助于解释在氧化应激动物中观察到的生理和行为变化。
