Hydrogen Sulfide Alleviates Lipid Peroxidation-Mediated Carbonyl Stress in Uranium-Intoxicated Kidney Cells via Nrf2/ARE Signaling.
- Author:
Jia Lin LIU
1
;
Min WANG
1
;
Rui ZHANG
1
;
Ji Fang ZHENG
1
;
Xi Xiu JIANG
1
;
Qiao Ni HU
1
Author Information
- Publication Type:Journal Article
- Keywords: Carbonyl stress; Hydrogen sulfide (H2S); Lipid peroxidation; Nephrotoxicity; Nrf2; Uranium
- MeSH: NF-E2-Related Factor 2/genetics*; Animals; Hydrogen Sulfide/pharmacology*; Rats; Signal Transduction/drug effects*; Lipid Peroxidation/drug effects*; Cell Line; Uranium/toxicity*; Antioxidant Response Elements; Kidney/metabolism*; Oxidative Stress/drug effects*; Cell Survival/drug effects*; Apoptosis/drug effects*
- From: Biomedical and Environmental Sciences 2025;38(4):484-500
- CountryChina
- Language:English
-
Abstract:
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 uranium-decreased 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 cycle-regulating mode through which H 2S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
