Department of Cardiology, Ningbo First Hospital, Ningbo, Zhejiang, 315000, China.
Department of Pharmacology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Biomed Res Int. 2022 May 25;2022:2416787. doi: 10.1155/2022/2416787. eCollection 2022.
Cold-inducible RNA-binding protein (CIRP) is a cellular stress-response protein, whose expression can be induced by a variety of stress conditions. Our previous study showed that intracellular CIRP is a protective factor against cellular oxidative stress and silencing of CIRP gene prone cells to apoptosis. However, the underlying mechanism remains unknown. The present study was aimed at investigating the possible mechanisms underlying the protective role of CIRP in oxidative stress injury. Herein, we used HEK293T cells as our cell model to investigate the relation between CIRP and the possible antioxidant pathways by using the latest genetic silencing technologies. Our results showed that silencing CIRP by using SaiRNA-based genetic silencing tool leads to the downregulation of Nrf2 and Nrf2-regulated antioxidant genes in HEK293T cells. Taken together, our study identified the antioxidant Nrf2 signaling pathway as a downstream target of CIRP, and silencing CIRP may prone cells to apoptosis by downregulating the Nrf2 antioxidant pathway in response to oxidative injury.
冷诱导 RNA 结合蛋白（CIRP）是一种细胞应激反应蛋白，其表达可被多种应激条件诱导。我们之前的研究表明，细胞内的 CIRP 是对抗细胞氧化应激的保护因子，沉默 CIRP 基因易导致细胞凋亡。然而，其潜在机制尚不清楚。本研究旨在探讨 CIRP 在氧化应激损伤中保护作用的潜在机制。本研究中，我们使用 HEK293T 细胞作为细胞模型，通过使用最新的基因沉默技术，探讨 CIRP 与可能的抗氧化途径之间的关系。结果表明，使用 SaiRNA 为基础的基因沉默工具沉默 CIRP 会导致 HEK293T 细胞中 Nrf2 和 Nrf2 调节的抗氧化基因下调。综上所述，本研究确定了抗氧化 Nrf2 信号通路是 CIRP 的下游靶点，沉默 CIRP 可能通过下调 Nrf2 抗氧化途径，使细胞对氧化损伤敏感，从而易导致细胞凋亡。
