National Primate Research Center, and Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Korea; Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea.
Disease Model Research Laboratory, Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.
BMB Rep. 2017 Oct;50(10):528-533. doi: 10.5483/bmbrep.2017.50.10.121.
Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16INK4a expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I-/- MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I-/- mice showed an increased number of cells with senescence associated-β-galactosidase (SA-β-gal) activity in a variety of tissues. Increased ROS levels and SA-β-gal activity, and reduction of chemical antioxidant further in Prx I-/- MEF supported an essential role of Prx I peroxidase activity in cellular senescence that is mediated by oxidative stress. The up-regulation of p16INK4a expression in Prx I-/- and suppression by overexpression of Prx I indicate that Prx I possibly modulate cellular senescence through ROS/p16INK4a pathway. [BMB Reports 2017; 50(10): 528-533].
过氧化物酶 I（Prx I）作为一种活性氧（ROS）清除剂，在保护和维持细胞内稳态方面发挥着重要作用；然而，其潜在的机制尚不清楚。在这里，我们发现 Prx I 通过抑制 p16INK4a 的表达在保护细胞免受 ROS 介导的细胞衰老方面起着关键作用。与野生型小鼠胚胎成纤维细胞（WT-MEFs）相比，Prx I-/- MEFs 表现出与衰老相关的表型。此外，衰老的 Prx I-/- 小鼠在多种组织中表现出具有衰老相关-β-半乳糖苷酶（SA-β-gal）活性的细胞数量增加。Prx I-/- MEF 中 ROS 水平和 SA-β-gal 活性的增加以及化学抗氧化剂的减少进一步支持了 Prx I 过氧化物酶活性在由氧化应激介导的细胞衰老中的重要作用。Prx I-/- 和过表达 Prx I 中 p16INK4a 表达的上调表明，Prx I 可能通过 ROS/p16INK4a 途径调节细胞衰老。[BMB 报告 2017；50(10): 528-533]。
