{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:39:33Z","timestamp":1760060373209,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Nature Science Foundation of China","award":["22276084","lzujbky-2022-32"],"award-info":[{"award-number":["22276084","lzujbky-2022-32"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["22276084","lzujbky-2022-32"],"award-info":[{"award-number":["22276084","lzujbky-2022-32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The rapid development of the nuclear industry and mining has increased environmental radioactive contamination, posing potentially ecological risks and health threats to humans. Uranium compounds are known to exhibit selective nephrotoxicity, but their toxicological processes and mechanisms still remain poorly understood and controversial. In this study, the uranyl-induced toxicity in human renal tubular epithelial cells (HK-2) were explored using flow cytometry, DAPI staining, and comet assays. Our results demonstrate that uranium exposure primarily triggers apoptosis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment and protein\u2013protein interaction (PPI) analyses revealed significant associations with DNA damage. Moreover, aberrant expression of ABC transporters (e.g., ABCB7) and mitochondrial-related proteins confirms uranium-induced mitochondrial dysfunction. Gene Ontology functional annotation implicated extrinsic apoptotic signaling pathways in uranium-induced cell death. The downregulation of the UBL5 protein also pointed to endoplasmic reticulum stress-mediated apoptosis. In summary, uranium exposure can induce the apoptosis of HK-2 cells through intrinsic pathways by damaging DNA and mitochondria and disrupting protein synthesis, with secondary contributions from endoplasmic reticulum stress and extrinsic apoptotic signaling.<\/jats:p>","DOI":"10.3390\/toxics13080699","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T15:53:37Z","timestamp":1755705217000},"page":"699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicological Mechanisms of Uranium-Induced Apoptosis in HK-2 Cells: A Proteomics and Metabolomics Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Zihuan","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxiang","family":"Huang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Song","sequence":"additional","affiliation":[{"name":"Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunling","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2254-5733","authenticated-orcid":false,"given":"Shirong","family":"Qiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1579\/0044-7447(2007)36[85:RSHRAH]2.0.CO;2","article-title":"Radon: Sources, health risks, and hazard mapping","volume":"36","author":"Appleton","year":"2007","journal-title":"Ambio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106107","DOI":"10.1016\/j.envint.2020.106107","article-title":"Emerging health risks and underlying toxicological mechanisms of uranium contamination: Lessons from the past two decades","volume":"145","author":"Ma","year":"2020","journal-title":"Environ. 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