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Zinc Protects Human Kidney Cells from Depleted Uranium‐induced Apoptosis
Author(s) -
Hao Yuhui,
Ren Jiong,
Liu Cong,
Li Hong,
Liu Jing,
Yang Zhangyou,
Li Rong,
Su Yongping
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12167
Subject(s) - apoptosis , cytochrome c , metallothionein , reactive oxygen species , chemistry , glutathione , caspase , catalase , caspase 3 , microbiology and biotechnology , programmed cell death , mitochondrion , fas ligand , oxidative stress , biology , zinc , biochemistry , enzyme , organic chemistry
Depleted uranium ( DU ) is a weak radioactive heavy metal, and zinc ( Z n) is an effective antidote to heavy metal poisoning. However, the effect of Z n on DU ‐induced cytotoxicity and apoptosis is not completely understood. The purpose of this study was to evaluate the effect of Z n on DU ‐induced cell apoptosis in human kidney cells ( HK ‐2) and explore its molecular mechanism. Pre‐treatment with Z n 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 F as receptor ( sF as R ) and soluble F as ligand ( sF as L ) 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 F as R ‐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, Z n inhibits DU ‐induced apoptosis.