Hydrogen Sulfide Alleviates Lipid Peroxidation-Mediated Carbonyl Stress in Uranium-Intoxicated Kidney Cells via Nrf2/ARE Signaling  

作　　者：Jialin Liu Min Wang Rui Zhang Jifang Zheng Xixiu Jiang Qiaoni Hu 

机构地区：[1]Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation,Faculty of Basic Medical Sciences,Guilin Medical University,Guilin 541004,Guangxi,China

出　　处：《Biomedical and Environmental Sciences》2025年第4期484-500,共17页生物医学与环境科学(英文版)

基　　金：supported by the National Natural Science Foundation of China(No.82160627);the Natural Science Foundation of the Guangxi Autonomous Region(No.2020GXNFSAA297262)。

摘　　要：Objective To explore the protective effects and underlying mechanisms of H_2S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.Methods Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2(Nrf2), and cystathionine β-synthase(CBS) expression were determined using western blotting or real-time PCR. Sulforaphane(SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression.Results GYY4137(an H_2S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uraniumdecreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes.Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability.Conclusion H_2S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H_2S axis. Simultaneously, the Nrf2-controlled CBS/H_2S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycleregulating mode through which H_2S attenuates the carbonyl stress-mediated NRK-52E cytotoxicit

关 键 词：Hydrogen sulfide(H_2S) Carbonyl stress Lipid peroxidation URANIUM NEPHROTOXICITY NRF2 

分 类 号：R285[医药卫生—中药学]