Fei Han , Ya Dong , Qiaoyan Liu , Linling Song , Hang Guo , Lingling Zhu , Bei Sun , Wei Zhao , Liming Chen
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引用次数: 0
Abstract
Protein S-nitrosylation (SNO), a redox-based posttranslational modification of cysteine thiols, plays a crucial role in various signaling pathways. Peroxiredoxin 2 (PRDX2) is one of the most potent ROS scavenging proteins, providing protection against oxidative stress damage, with its function regulated by SNO. However, the precise role of SNO-PRDX2 in hyperuricemic nephropathy remains poorly understood. In this study, we identified PRDX2 as a highly S-nitrosylated target in hyperuricemic nephropathy using a biotin switch assay. The elevation of SNO-PRDX2 was observed in kidneys of hyperuricemic mice as well as in uric acid (UA)-treated human renal tubular epithelial (HK-2) cells. S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, induced SNO modification of PRDX2, promoting mitochondrial dysfunction, oxidative stress, and cell apoptosis in HK-2 cells. Transfection with a plasmid containing a mutated cysteine 172 (Cys172) of PRDX2 yielded a decrease in SNO-PRDX2 levels in both hyperuricemic mice and UA-cultured HK-2 cells. Furthermore, administration of adeno-associated viruses carrying the Cys172-mutated PRDX2 significantly ameliorated renal interstitial fibrosis and reduced mitochondrial dysfunction, oxidative stress, and cell apoptosis in HUA-treated mice. In conclusion, our findings indicate that SNO modification of PRDX2 at Cys172 mediates HUA-induced kidney interstitial fibrosis, suggesting that SNO-PRDX2 may serve as a potential therapeutic target for HUA-induced renal injury.
期刊介绍:
Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.