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Vanadate-induced cell death is dissociated from H2O2 generation

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Abstract

Vanadium is an environmentally toxic metal with peculiar and sometimes contradictory cellular effects. It is insulin-mimetic, it can either stimulate cell growth or induce cell death, and it has both mutagenic and antineoplastic properties. However, the mechanisms involved in those effects are poorly understood. Several studies suggest that H2O2 is involved in vanadate-induced cell death, but it is not known whether cellular sensitivity to vanadate is indeed related to H2O2 generation. In the present study, the sensitivity of four cell lines from different origins (K562, K562-Lucena 1, MDCK, and Ma104) to vanadate and H2O2 was evaluated and the production of H2O2 by vanadate was analyzed by flow cytometry. We show that cell lines very resistant to H2O2 (K562, K562-Lucena 1, and Ma104 cells) are much more sensitive to vanadate than MDCK, a cell line relatively susceptible to H2O2, suggesting that vanadate-induced cytotoxicity is not directly related to H2O2 responsiveness. In accordance, vanadate concentrations that reduced cellular viability to approximately 60–70% of the control (10 μmol/L) did not induce H2O2 formation. A second hypothesis, that peroxovanadium (PV) compounds, produced once vanadate enters into the cells, are responsible for the cytotoxicity, was only partially confirmed because MDCK cells were resistant to both vanadate and PV compounds (10 μmol/L each). Therefore, our results suggest that vanadate toxicity occurs by two distinct pathways, one dependent on and one independent of H2O2 production.

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Abbreviations

DHR:

dihydrorhodamine 123

PTP:

phosphotyrosine phosphatase

PV:

peroxovanadium

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Authors and Affiliations

  1. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS - Bloco G, 21949-900, Rio de Janeiro, RJ, Brazil

    M. A. M. Capella, L. S. Capella, M. Gefé & A. G. Lopes

  2. Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    R. C. Valente

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  1. M. A. M. Capella
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  2. L. S. Capella
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  3. R. C. Valente
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  4. M. Gefé
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  5. A. G. Lopes
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Correspondence to M. A. M. Capella.

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Capella, M.A.M., Capella, L.S., Valente, R.C. et al. Vanadate-induced cell death is dissociated from H2O2 generation. Cell Biol Toxicol 23, 413–420 (2007). https://doi.org/10.1007/s10565-007-9003-4

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  • DOI: https://doi.org/10.1007/s10565-007-9003-4

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