Selenium modulates oxidative stress-induced cell apoptosis in human myeloid HL-60 cells through regulation of calcium release and caspase-3 and -9 activities.
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 Ca(2+) mobilization, cell viability and caspase-3 and -9 activities at different sample times. We found the toxic concentration and toxic time of H(2)O(2) as 100 microM: and 10 h on cell viability in the cells using four different concentrations of H(2)O(2) (1 microM: -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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
Uğuz
Abdülhadi Cihangir
AC
Department of Physiology, University of Extremadura, Badajoz, Spain.
Naziroğlu
Mustafa
M
Espino
Javier
J
Bejarano
Ignacio
I
González
David
D
Rodríguez
Ana Beatriz
AB
Pariente
Jose Antonio
JA
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology*; D012643:Selenium / Q000494:pharmacology*
D006861:Hydrogen Peroxide; D053148:Caspase 3; D053453:Caspase 9; D012643:Selenium; D002118:Calcium