Moriwaki Takahito, Yoshimura Akari, Tamari Yuki, Sasanuma Hiroyuki, Takeda Shunichi, Seki Masayuki, Tano Keizo
Department of Molecular and Genetic Medicine, Kawasaki Medical School, 577, Matsushima, Kurashiki-city, Okayama, 701-0192, Japan.
Division of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan.
Genes Environ. 2021 Aug 5;43(1):35. doi: 10.1186/s41021-021-00211-4.
Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study.
The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS.
PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.
过氧化物酶1（PRDX1）是普遍存在的硫醇过氧化物酶家族的成员，该家族催化包括过氧化氢在内的过氧化物的还原反应。它作为一种抗氧化酶发挥作用，类似于过氧化氢酶和谷胱甘肽过氧化物酶。最近研究表明PRDX1可作为活性氧（ROS）的传感器，并在依赖ROS的细胞内信号通路中发挥作用。为了研究其生理功能，在本研究中在鸡DT40细胞中对PRDX1进行了条件性敲除。
PRDX1的缺失导致细胞死亡，细胞内ROS水平升高。PRDX1缺失的细胞未显示出染色体断裂或姐妹染色单体交换（SCE）的积累。这些结果表明PRDX1缺失的细胞中的细胞死亡不是由于DNA损伤。2-巯基乙醇可保护PRDX1缺失的细胞免于细胞死亡，并也抑制ROS的升高。
PRDX1在鸡DT40细胞中是必需的，并且在维持细胞内ROS稳态（或在细胞ROS水平的微调）中起重要作用。缺乏PRDX1的细胞可作为内源性失调的ROS模型，以阐明ROS在维持适当细胞生长中的生理作用。
