三个对“氧化应激”的重新认识  

Three New Understandings of Oxidative Stress

作　　者：陈畅[1] CHEN Chang(Key Laboratory of Biomacromolecules(CAS),National Laboratory of Biomacromolecules,CAS,Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China)

机构地区：[1]中国科学院生物物理研究所,生物大分子重点实验室,北京100101

出　　处：《生物化学与生物物理进展》2024年第10期2292-2297,共6页Progress In Biochemistry and Biophysics

基　　金：国家重点研发计划(2022YFA1303000);中国科学院战略性先导科技专项(B类)(XDB39000000)资助。

摘　　要：生命离不开氧,细胞的氧化还原状态直接调控蛋白质等生物大分子功能,介导细胞信号转导以及衰老、神经退行性疾病、代谢病、肿瘤等许多生理和病理过程。鉴于20世纪50年代提出的自由基衰老学说,长期以来氧化应激常与氧化损伤混为一谈,“抗氧化”一度成为“抗衰老”的代名词。本文结合本实验室相关研究工作及领域前沿,提出三个对“氧化应激”的重新认识:第一,氧化应激不等于氧化损伤,具有重要生理功能;第二,氧化应激不是“万金油”,氧化还原调控具有特异性,氧化还原修饰是其作用机制;第三,不能泛泛抗氧化,氧化还原平衡具有精准属性,抗氧化要考虑5R(Right species,Right place,Right time,Right level,Right target)原则,精准氧化还原医药时代已开启。未来挑战体现在氧化还原生物学与医学基础研究、氧化应激在生理和病理过程及环境胁迫中的特异分子机制研究及精准氧化还原干预三大方面,需要多学科交叉、基础与临床研究深度合作、国际协同攻关,实现对生命过程氧化还原认识的突破、机理的突破、精准干预的突破!Life is inseparable from oxygen.The redox state in cells directly regulates the functions of biomacromolecules and mediates cell signal transduction and many physiological and pathological processes such as aging,neurodegenerative diseases,cardiovascular diseases,metabolic diseases,and tumors.In view of The Free Radical Theory of Aging proposed in the 1950s,oxidative stress has long been confused with oxidative damage and is regarded as bad.Antioxidation once became synonymous of“anti-aging”.Here in combination the relevant research work of our laboratory and the frontiers of the redox biology field,we propose three new understandings of“oxidative stress”.(1)Oxidative stress is not equal to oxidative damage and has important physiological functions.(2)Oxidative stress is not related to all physiological and pathological processes without specificity,while redox regulation is specific and redox modification of biomacromolecules is the mechanism.(3)Non-targeting antioxidants do not work well,the redox balance has precise properties,5R principle should be considered for antioxidant pharmacology and the new era of precision redox medicine has begun.Future challenges are reflected in three major aspects:basic research on redox biology and medicine,the specific molecular mechanisms of oxidative stress in physiological and pathological processes and environmental stress,and precise redox intervention against aging and diseases.Multidisciplinary basic research,in-depth cooperation between basic research and clinical research and international collaboration must be enhanced to achieve breakthroughs in the understanding of redox in life processes,breakthroughs in redox mechanisms,and breakthroughs in precision intervention!

关 键 词：氧化应激 氧化损伤 氧化还原修饰 精准氧化还原 5R原则 抗氧化 衰老 

分 类 号：Q28[生物学—细胞生物学] Q255