1,25-(OH) 2 D 3 improves SD rats high-altitude pulmonary edema by inhibiting ferroptosis and ferritinophagy in alveolar epithelial cells.

Autor: Wang Y; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: wyxpzf1999@163.com., Su H; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: suhong807@163.com., Lin X; Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610000, China. Electronic address: linxue0926@foxmail.com., Dai C; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: daichongyang09@163.com., Cheng Q; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: cchnqian@163.com., Deng Z; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: 284131098@qq.com., Yang Y; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: yguo8075@gmail.com., Pu X; Qinghai University, Xining, Qinghai Province 810016, China. Electronic address: puxiaoyan1975@163.com.
Jazyk: angličtina
Zdroj: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2024 Dec 15; Vol. 247, pp. 106663. Date of Electronic Publication: 2024 Dec 15.
DOI: 10.1016/j.jsbmb.2024.106663
Abstrakt: Background: This study investigates the protective effects and potential mechanisms of 1,25-(OH) 2 D 3 against high-altitude pulmonary edema (HAPE).
Methods: Hypoxia-induced rats were administered 1,25-(OH) 2 D 3 for 24, 48, and 72 hours, and we observed lung tissue injury and pulmonary edema. Immunohistochemistry (IHC) and Western blot analyses were employed to analyze the expression of markers associated with ferroptosis and ferritinophagy in rat lungs. Metabolomics analysis was conducted to investigate changes in serum lipid metabolites. We validated the mechanism of action of 1,25-(OH) 2 D 3 in type II alveolar epithelial cells induced by hypoxia.
Results: Our results demonstrated that hypoxic exposure significantly altered sodium-water transport in the lungs, leading to edema formation. The degree of pulmonary edema was most pronounced at 48 hours of hypoxi. Treatment with 1,25-(OH) 2 D 3 improved lung function and reduced the degree of pulmonary edema in hypoxic rats. Hypoxia-induced increases in 4-HNE and MDA levels in the lungs, along with iron accumulation, were observed. Hypoxia also resulted in elevated levels of NCOA4, LC3Ⅱ, and FTH1 proteins in the lungs. Furthermore, treatment with 1,25-(OH) 2 D 3 significantly inhibited ferroptosis and ferritinophagy in the lungs after hypoxia. The levels of lipid metabolites, such as L-Aspartic acid and L-Fucose, were significantly elevated in the serum of hypoxic rats. After 1,25-(OH) 2 D 3 treatment, these levels exhibited a significant reduction.
Conclusion: In hypoxic type II alveolar epithelial cells, 1,25-(OH) 2 D 3 improved hypoxia-induced sodium-water transport, ferroptosis, and ferritinophagy, which were reversed by the autophagy agonist Rapamycin.By modulating ferroptosis and ferritinophagy, 1,25-(OH) 2 D 3 mitigated the deleterious effects of hypoxia on pulmonary function.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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