Wu Yifan, Xv Yuanyuan, Zhao Limei, Zhou Ziqi, Wang Miaomiao, Xi Jima, Liming Ying, Gao Jianling, Deng Bingqing, Zheng Dong
Department of Pathology and Pathophysiology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Department of Thoracic Surgery, School of Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Physiol Rep. 2025 Jan;13(1):e70162. doi: 10.14814/phy2.70162.
Cisplatin is a widely used anticancer drug, but its accumulation in renal tubular epithelial cells (TECs) can cause acute kidney injury. Phosphoseryl-tRNA kinase (PSTK) is an intermediate product produced under oxidative stress conditions. This study aimed to elucidate whether PSTK could protect TECs and its possible mechanisms. We found that PSTK levels decreased after cisplatin treatment, but PSTK overexpression using lentivirus vectors protected TEC viability. Overexpression of PSTK increased selenoprotein concentrations and reduced intracellular ROS levels. Additionally, PSTK overexpression inhibited the BAX/BCL2/Caspase 3 pathway after cisplatin stimulation, suggesting its potential role in preventing cell apoptosis. Taken together, this study suggests that PSTK could protect TEC viability from cisplatin-induced injury, possibly by inhibiting mitochondrial apoptosis. The study is significant for developing therapeutic strategies that could manipulate PSTK to delay AKI progression.
顺铂是一种广泛使用的抗癌药物，但其在肾小管上皮细胞（TECs）中的蓄积可导致急性肾损伤。磷酸丝氨酰 - tRNA激酶（PSTK）是在氧化应激条件下产生的中间产物。本研究旨在阐明PSTK是否能保护TECs及其可能的机制。我们发现顺铂处理后PSTK水平降低，但使用慢病毒载体过表达PSTK可保护TECs的活力。PSTK的过表达增加了硒蛋白浓度并降低了细胞内活性氧水平。此外，PSTK过表达在顺铂刺激后抑制了BAX/BCL2/半胱天冬酶3通路，表明其在预防细胞凋亡中的潜在作用。综上所述，本研究表明PSTK可能通过抑制线粒体凋亡来保护TECs活力免受顺铂诱导的损伤。该研究对于制定可操控PSTK以延缓急性肾损伤进展的治疗策略具有重要意义。
