Prdx1-KO Mouse

Prdx1, short for peroxiredoxin 1, is a member of the peroxidase family. It functions primarily in protecting cells against damage caused by H₂O₂, acting as an antioxidant enzyme. It is also involved in multiple cellular signaling pathways, including those related to NF-κB activation, autophagy, and redox-regulation, which are crucial for maintaining cellular homeostasis and are associated with various biological processes and diseases [1].

In colorectal cancer, PRDX1 knockout mice showed a significant decrease in the number of AOM/DSS-induced colitis-associated CRC, accompanied by downregulation of NRF2 and GPX4. Mechanistically, knockdown of PRDX1 led to ROS-induced mitochondrial dysfunction and lipid peroxidation-induced ferroptosis in CRC cells, suggesting that PRDX1 promotes CRC progression by suppressing CUL3-mediated NRF2 degradation [2]. In glioma cells, radiation-induced IRAK1 binds to PRDX1, preventing its ubiquitination and degradation by E3 ubiquitin ligase HECTD3. Overexpression of PRDX1 reverses the radiotherapy sensitization effect of IRAK1 depletion by diminishing autophagic cell death, indicating the IRAK1-PRDX1 axis as a potential therapeutic target [3].

In conclusion, Prdx1 is essential for antioxidant defense, redox-regulation, and the modulation of multiple signaling pathways. The use of Prdx1 knockout mouse models has provided valuable insights into its role in diseases such as colorectal cancer and glioma, highlighting its potential as a therapeutic target. Understanding Prdx1's functions can help in developing new strategies for treating these diseases.

References:

1. Guan, Xin, Ruan, Yiyin, Che, Xiaoxia, Feng, Weiwei. 2023. Dual role of PRDX1 in redox-regulation and tumorigenesis: Past and future. In Free radical biology & medicine, 210, 120-129. doi:10.1016/j.freeradbiomed.2023.11.009. https://pubmed.ncbi.nlm.nih.gov/37977211/

2. Song, Yujia, Wang, Xiaohui, Sun, Yuqi, Qu, Xianjun, Yu, Xinfeng. 2024. PRDX1 inhibits ferroptosis by binding to Cullin-3 as a molecular chaperone in colorectal cancer. In International journal of biological sciences, 20, 5070-5086. doi:10.7150/ijbs.99804. https://pubmed.ncbi.nlm.nih.gov/39430237/

3. Li, Jing, Sun, Yuchen, Zhao, Xu, Sun, Xuanzi, Zhang, Xiaozhi. 2023. Radiation induces IRAK1 expression to promote radioresistance by suppressing autophagic cell death via decreasing the ubiquitination of PRDX1 in glioma cells. In Cell death & disease, 14, 259. doi:10.1038/s41419-023-05732-0. https://pubmed.ncbi.nlm.nih.gov/37031183/