title: Zinc protects human kidney cells from depleted uranium-induced apoptosis.
abstract: Depleted uranium (DU) is a weak radioactive heavy metal, and zinc (Zn) is an effective antidote to heavy metal poisoning. However, the effect of Zn on DU-induced cytotoxicity and apoptosis is not completely understood. The purpose of this study was to evaluate the effect of Zn on DU-induced cell apoptosis in human kidney cells (HK-2) and explore its molecular mechanism. Pre-treatment with Zn significantly inhibited DU-induced apoptosis. It reduced the formation of reactive oxygen species in the cells, increased the catalase (CAT) and glutathione (GSH) concentrations, suppressed the DU-induced soluble Fas receptor (sFasR) and soluble Fas ligand (sFasL) overexpression, suppressed the release of cytochrome c and apoptosis inhibitor factor (AIF) from mitochondria to cytoplasm, inhibited the activation of caspase-9, caspase-8 and caspase-3, and induced metallothionein (MT) expression. Furthermore, exogenous MT effectively inhibited DU-induced cell apoptosis. In conclusion, mitochondrial and FasR-mediated apoptosis pathways contribute to DU-induced apoptosis in HK-2 cells. Through independent mechanisms, such as indirect antioxidant effects, inhibition of the activation of caspase-9, caspase-8 and caspase-3, and induction of MT expression, Zn inhibits DU-induced apoptosis.
authors: State Key Laboratory of Trauma Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Shapingba, Chongqing, China.
authors: Yuhui
authors: Y
authors: Hao
authors: Jiong
authors: J
authors: Ren
authors: Cong
authors: C
authors: Liu
authors: Hong
authors: H
authors: Li
authors: Jing
authors: J
authors: Liu
authors: Zhangyou
authors: Z
authors: Yang
authors: Rong
authors: R
authors: Li
authors: Yongping
authors: Y
authors: Su
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D008668:Metallothionein / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014501:Uranium / Q000506:poisoning*; D015032:Zinc / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019014:fas Receptor; D014501:Uranium; D008668:Metallothionein; D002374:Catalase; D020169:Caspases; D005978:Glutathione; D015032:Zinc