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Selenium Modulates Oxidative Stress-Induced Cell Apoptosis in Human Myeloid HL-60 Cells Through Regulation of Calcium Release and Caspase-3 and -9 Activities

Abstract

Selenium is an essential chemopreventive antioxidant element to oxidative stress, although high concentrations of selenium induce toxic and oxidative effects on the human body. However, the mechanisms behind these effects remain elusive. We investigated toxic effects of different selenium concentrations in human promyelocytic leukemia HL-60 cells by evaluating Ca2+ mobilization, cell viability and caspase-3 and -9 activities at different sample times. We found the toxic concentration and toxic time of H2O2 as 100 μm and 10 h on cell viability in the cells using four different concentrations of H2O2 (1 μm–1 mm) and six different incubation times (30 min, 1, 2, 5, 10, 24 h). Then, we found the therapeutic concentration of selenium to be 200 nm by cells incubated in eight different concentrations of selenium (10 nm–1 mm) for 1 h. We measured Ca2+ release, cell viability and caspase-3 and -9 activities in cells incubated with high and low selenium concentrations at 30 min and 1, 2, 5, 10 and 24 h. Selenium (200 nm) elicited mild endoplasmic reticulum stress and mediated cell survival by modulating Ca2+ release, the caspases and cell apoptosis, whereas selenium concentrations as high as 1 mm induced severe endoplasmic reticulum stress and caused cell death by activating modulating Ca2+ release, the caspases and cell apoptosis. In conclusion, these results explained the molecular mechanisms of the chemoprotective effect of different concentrations of selenium on oxidative stress-induced apoptosis.

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Acknowledgements

J. A. P. and M. N. formulated the present hypothesis and were responsible for writing the report. A. C. U., J. E., I. B., D. G. and A. B. R. were responsible analyses the data. J. A. P. and M. N. made critical revisions to the manuscript.

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Correspondence to Mustafa Nazıroğlu.

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Uğuz, A.C., Nazıroğlu, M., Espino, J. et al. Selenium Modulates Oxidative Stress-Induced Cell Apoptosis in Human Myeloid HL-60 Cells Through Regulation of Calcium Release and Caspase-3 and -9 Activities. J Membrane Biol 232, 15 (2009). https://doi.org/10.1007/s00232-009-9212-2

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Keywords

  • Selenium
  • Endoplasmic reticulum stress
  • Apoptosis
  • Oxidative stress