Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, 605014, India.
Biogerontology. 2021 Feb;22(1):81-100. doi: 10.1007/s10522-020-09904-9. Epub 2020 Oct 27.
Reactive oxygen species (ROS) have long been found to play an important role in oxidative mediated DNA damage. Fortunately, cells possess an antioxidant system that can neutralize ROS. However, oxidative stress occurs when antioxidants are overwhelmed by ROS or impaired antioxidant pathways. This study was carried out to find the protective effect of astaxanthin on the yeast DNA repair-deficient mutant cells under hydrogen peroxide stress. The results showed that astaxanthin enhances the percent cell growth of rad1∆, rad51∆, apn1∆, apn2∆ and ogg1∆ cells. Further, the spot test and colony-forming unit count results confirmed that astaxanthin protects DNA repair mutant cells from oxidative stress. The DNA binding property of astaxanthin studied by in silico and in vitro methods indicated that astaxanthin binds to the DNA in the major and minor groove, and that might protect DNA against oxidative stress induced by Fenton's reagent. The intracellular ROS, 8-OHdG level and the DNA fragmentation as measured by comet tail was reduced by astaxanthin under oxidative stress. Similarly, reduced nuclear fragmentation and chromatin condensation results suggest that astaxanthin might reduce apoptosis. Finally, we show that astaxanthin decreases the accumulation of mutation rate and enhances the longevity of DNA repair-deficient mutants' cells during a chronological lifespan.
活性氧(ROS)长期以来被发现对氧化介导的 DNA 损伤起着重要作用。幸运的是,细胞拥有一种抗氧化系统,可以中和 ROS。然而,当抗氧化剂被 ROS 淹没或抗氧化途径受损时,就会发生氧化应激。本研究旨在寻找虾青素在过氧化氢应激下对酵母 DNA 修复缺陷突变细胞的保护作用。结果表明,虾青素增强了 rad1∆、rad51∆、apn1∆、apn2∆ 和 ogg1∆ 细胞的细胞生长百分比。此外,点测试和集落形成单位计数结果证实虾青素可保护 DNA 修复突变细胞免受氧化应激。通过计算机模拟和体外方法研究虾青素的 DNA 结合特性表明,虾青素与 DNA 的大沟和小沟结合,这可能保护 DNA 免受 Fenton 试剂诱导的氧化应激。在氧化应激下,虾青素降低了细胞内 ROS、8-OHdG 水平和彗星尾的 DNA 片段化。同样,减少核片段化和染色质浓缩的结果表明虾青素可能减少细胞凋亡。最后,我们表明虾青素可以减少突变率的积累,并在酵母的时序寿命过程中提高 DNA 修复缺陷突变体细胞的寿命。