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Vanadate induces apoptosis in epidermal JB6 Pplus cells via hydrogen peroxide-mediated reactions

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Abstract

Apoptosis is a physiological mechanism for the control of DNA integrity in mammalian cells. Vanadium induces both DNA damage and apoptosis. It is suggested that vanadium-induced apoptosis serves to eliminate DNA-damaged cells. This study is designed to clarify a role of reactive oxygen species in the mechanism of apoptosis induced by vanadium. We established apoptosis model with murine epidermal JB6 P+ cells in the response to vanadium stimulation. Apoptosis was detected by a cell death ELISA assay and morphological analysis. The result shows that apoptosis induced by vanadate is dose-dependent, reaching its saturation level at a concentration of 100 μM vanadate. Vanadyl (IV) can also induce apoptosis albeit with lesser potency. A role of reactive oxygen species was analyzed by multiple reagents including specific scavengers of different reactive oxygen species. The result shows that vanadate-induced apoptosis is enhanced by NADPH, superoxide dismutase and sodium formate, but was inhibited by catalase and deferoxamine. Cells exposed to vanadium consume more molecular oxygen and at the same time, produce more H2O2 as measured by the change in fluorescence of scopoletin in the presence of horseradish peroxidase. This change in oxygen consumption and H2O2 production is enhanced by NADPH. Taken together, these results show that vanadate induces apoptosis in epidermal cells and H2O2 induced by vanadate plays a major role in this process.

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Authors and Affiliations

  1. Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, W, 26505, USA

    Jianping Ye, Min Ding, Stephen S. Leonard, Victor A. Robinson, Lyndell Millecchia, Xiaoying Zhang, Vince Castranova, Val Vallyathan & Xianglin Shi

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  1. Jianping Ye
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  2. Min Ding
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  3. Stephen S. Leonard
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  4. Victor A. Robinson
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  5. Lyndell Millecchia
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  7. Vince Castranova
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  8. Val Vallyathan
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  9. Xianglin Shi
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Ye, J., Ding, M., Leonard, S.S. et al. Vanadate induces apoptosis in epidermal JB6 Pplus cells via hydrogen peroxide-mediated reactions. Mol Cell Biochem 202, 9–17 (1999). https://doi.org/10.1023/A:1007078915585

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