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Chemical and biological insights into uranium-induced apoptosis of rat hepatic cell line

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Abstract

Ur anium release into the environment is a threat to human health, and the mechanisms of cytotoxicity caused by uranium are not well-understood. To improve our understanding in this respect, we herein evaluated the effects of uranium exposure on normal rat hepatic BRL cells. As revealed by scanning electron microscopy and transmission electron microscope analysis, uranyl nitrate was found to be transformed into uranyl phosphate particles in the medium and taken up by BRL cells in an endocytotic uptake manner, which presumably initiates apoptosis of the cell, although soluble uranyl ion may also be toxic. The apoptosis of BRL cells upon uranium exposure was also confirmed by both the acridine orange and ethidium bromide double staining assay and the Annexin V/propidium iodide double staining assay. Further studies revealed that uranium induced the loss of mitochondrial membrane potential in a dose-dependent manner. Moreover, the uranium-induced apoptosis was found to be associated with the activation of caspase-3, caspase-8 and caspase-9, indicating both a mitochondria-dependent signaling pathway and a death receptor pathway by a crosstalk. This study provides new chemical and biological insights into the mechanism of uranium toxicity toward hepatic cells, which will help seek approaches for biological remediation of uranium.

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Acknowledgments

This study was supported by Natural Science Foundation of China (Nos. 21101091; 21171007), the construct program of the key discipline in Hunan province (No. [2011]76) and the developing program of science and technology of Hengyang city (No. 2013KJ17).

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Authors and Affiliations

  1. Key Laboratory of Tumor Cellular and Molecular Pathology, University of South China, College of Hunan Province, Hengyang, 421001, China

    Fang Liu, Yong You & Ge-Bo Wen

  2. School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, China

    Ke-Jie Du & Ying-Wu Lin

  3. College of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241000, China

    Zhen Fang

  4. Laboratory of Protein Structure and Function, University of South China, Hengyang, 421001, China

    Ge-Bo Wen & Ying-Wu Lin

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  1. Fang Liu
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  2. Ke-Jie Du
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  3. Zhen Fang
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Correspondence to Ge-Bo Wen or Ying-Wu Lin.

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Liu, F., Du, KJ., Fang, Z. et al. Chemical and biological insights into uranium-induced apoptosis of rat hepatic cell line. Radiat Environ Biophys 54, 207–216 (2015). https://doi.org/10.1007/s00411-015-0588-3

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  • DOI: https://doi.org/10.1007/s00411-015-0588-3

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