Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems.

Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems.
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DOI:
10.1111/j.1582-4934.2009.00897.x
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发表时间:
2010-04
影响因子:
5.3
通讯作者:
Chen C
Chen C
中科院分区:
医学2区
文献类型:
--
作者:
Lü JM;Lin PH;Yao Q;Chen C

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生物系统中氧、氮、硫等分子产生的自由基,由于具有不成对电子,与其他分子反应时具有很高的活性。这些自由基是称为活性氧/氮类(ROS/RNS)的分子组的重要部分,其在细胞代谢和功能活动期间产生,并且在细胞信号传导、凋亡、基因表达和离子转运中具有重要作用。然而,过量的ROS会攻击核酸中的碱基、蛋白质中的氨基酸侧链和不饱和脂肪酸中的双键,并引起氧化应激,这会损伤DNA、RNA、蛋白质和脂质,导致心血管疾病、癌症、自闭症和其他疾病的风险增加。细胞内的抗氧化酶和膳食抗氧化剂的摄入可能有助于维持体内足够的抗氧化状态。在过去的几十年里,人们建立了新的分子技术、细胞培养和动物模型来研究抗氧化剂对ROS的影响和机制。化学和分子方法已被用于研究抗氧化剂的机制和动力学,并确定新的有效的抗氧化剂。抗氧化剂可通过与自由基反应直接降低氧化损伤,或通过抑制自由基产生酶的活性或表达或增强细胞内抗氧化酶的活性或表达间接降低氧化损伤。新的化学和无细胞生物系统已被应用于解剖抗氧化剂的分子作用。本文综述了氧化应激和抗氧化剂在脂质过氧化、DNA损伤、蛋白质修饰以及酶活性等方面的研究进展,重点介绍了化学和无细胞生物系统。
Free radicals derived from oxygen, nitrogen and sulphur molecules in the biological system are highly active to react with other molecules due to their unpaired electrons. These radicals are important part of groups of molecules called reactive oxygen/nitrogen species (ROS/RNS), which are produced during cellular metabolism and functional activities and have important roles in cell signalling, apoptosis, gene expression and ion transportation. However, excessive ROS attack bases in nucleic acids, amino acid side chains in proteins and double bonds in unsaturated fatty acids, and cause oxidative stress, which can damage DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and intake of dietary antioxidants may help to maintain an adequate antioxidant status in the body. In the past decades, new molecular techniques, cell cultures and animal models have been established to study the effects and mechanisms of antioxidants on ROS. The chemical and molecular approaches have been used to study the mechanism and kinetics of antioxidants and to identify new potent antioxidants. Antioxidants can decrease the oxidative damage directly via reacting with free radicals or indirectly by inhibiting the activity or expression of free radical generating enzymes or enhancing the activity or expression of intracellular antioxidant enzymes. The new chemical and cell-free biological system has been applied in dissecting the molecular action of antioxidants. This review focuses on the research approaches that have been used to study oxidative stress and antioxidants in lipid peroxidation, DNA damage, protein modification as well as enzyme activity, with emphasis on the chemical and cell-free biological system.
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