兰州大学机构库 >生命科学学院
多酚类抗氧化剂在化学系统和细胞体系中都能快速修复DNA损伤
Alternative TitleFast Repair of Polyphenolic Antioxidants on DNA Damage in vitro and in vivo
赵晨阳
Thesis Advisor郑荣梁
2003-05-12
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword多酚类抗氧化剂 修复
Abstract本工作发现多酚类抗氧化剂可保护DNA,它可通过下列三种机制来实现:(1)多酚类化合物苯丙素甙(PPGs)可以通过络合铁离子抑制Fenton反应,从根本上制止活性氧的生成;(2)多酚类化合物芦丁、槲皮素、苯丙素甙及其类似物除了能清除活性氧外,还能清除 NO 的体内代谢产物CO3.-和 NO2.,从而避免了ROS/RNS对DNA的损伤。测得被试多酚与CO3.-和NO2.的反应速率常数分别为:1.9 - 3.4 × 108 mol-1.L.s-1和 0.11 - 1.9 × 108 mol-1.L.s-1;(3)当DNA受到ROS/RNS攻击而损伤后,芦丁和槲皮素可快速修复DNA的多种损伤,测得对dGMP羟基加合物、dGMP、dAMP、dCMP和poly C阳离子自由基、dT阴离子自由基的修复反应速率常数分别为 1.31 - 4.4 × 108 mol-1.L.s-1和 1.5 - 8.8 × 108 mol-1.L.s-1。结合我组从前的工作,说明多酚类对 DNA 氧化性损伤的修复作用具有普遍性。普遍性表现之一:不仅PPG而且其它多种酚类都可以快速修复DNA损伤;普遍性表现之二:DNA的四种碱基、核苷、核苷酸、多聚核苷酸和单双链DNA等多种结构层次上的DNA损伤都可被快速修复。且修复反应可在微秒级时间范围内完成,比酶性修复快八九个数量级,从而有效阻止了 DNA 瞬态损伤产物与其它生物大分子的进一步反应。 首次证明在细胞体系中也存在快速修复作用。利用竞争反应原理造成胞内DNA的瞬态损伤,这时多酚类抗氧化剂可在DNA的酶性修复系统启动之前显著降低细胞 DNA 期外合成、DNA 碱基稳态损伤产物8-OH-dG 的生成和 DNA 的断链程度。由于没有酶性修复系统的参与,因此上述三种 DNA 损伤指标的显著下降反映了多酚类化合物在细胞内也发挥了快速修复作用,表明多酚类无论在化学系统或细胞中都能快速修复DNA损伤,这也就是普遍性表现之三。 本工作揭示了多酚类抗氧化剂的系统作用机制,它有助于促进对自由基相关疾病的防治。
Other AbstractIn the present work, it is shown that (1) phenylpropanoid glycoside (PPG, one of polyphenols) is able to protect DNA by chelating metal ions, thereby to inhibit Fenton reaction and the formation of reactive oxygen species (ROS); (2) polyphenols, such as rutin, quercetin, PPG and its analogs are able to scavenge not only ROS, but also RNS such as CO3.- and NO2., which are the metabolic products of NO., the rate constants of scavenging reaction of CO3.- and NO2. by tested phenols were determined to be 1.9 - 3.4 × 108 mol-1 . L. s-1 and 0.11 - 1.9 × 108 mol-1. L.s-1 respectively; (3) The DNA damage such as hydroxyl radical adduct of dGMP, the cation radicals of dGMP, dAMP, dCMP and poly C, the anion radical of dT, all of them can be fast repaired by quercetin and rutin, the rate constants of fast repair reactions of the DNA radicals were determined to be 1.31 - 4.4 × 108 mol-1 . L. s-1 by quercetin and 1.5 - 8.8 × 108 mol-1 . L . s-1 by rutin respectively. Together with findings from our previous studies, the present results demonstrate that fast repair is the universal activity of polyphenolic antioxidants against DNA damage. The universality is exhibited by (1) not only PPGs but also other polyphenols can fast repair DNA damage; (2) polyphenols can fast repair DNA damage in all the different structural levels, including bases, nucleosides, nucleotides, polynucleotides and single or double strands DNA. Furthermore, the repair reaction should finish in the time scale of microsecond, the reaction rate is much higher than that of enzymatic repair for 8-9 orders, therefore, preventing the DNA transient damage to further attack other biomolecules.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221521
Collection生命科学学院
Recommended Citation
GB/T 7714
赵晨阳. 多酚类抗氧化剂在化学系统和细胞体系中都能快速修复DNA损伤[D]. 兰州. 兰州大学,2003.
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