Selenite negatively regulates caspase-3 through a redox mechanism

Hee Sae Park, Sung-Ho Huh, Youngho Kim, Jaekyung Shim, Seung Hoon Lee, Il Seon Park, Yong Keun Jung, Ick Young Kim, Eui Ju Choi

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Selenium, an essential biological trace element, exerts its modulatory effects in a variety of cellular events including cell survival and death. In our study we observed that selenite protects HEK293 cells from cell death induced by ultraviolet B radiation (UVB). Exposure of HEK293 cells to UVB radiation resulted in the activation of caspase-3-like protease activity, and pretreatment of the cells with z-DEVD-fmk (N-benzyloxycarbonyl-Asp-Glu-Val- Asp-fluoromethylketone), a caspase-3 inhibitor, prevented UVB-induced cell death. Interestingly, enzymatic activity of caspase-3-like protease in cell lysates of UVB-exposed cells was repressed in vitro by the presence of selenite. Selenite also inhibited the in vitro activity of purified recombinant caspase-3 in cleaving Ac-DEVD-pNA (N-acetyl-Asp-Glu-Asp-p- nitroanilide) or ICAD(L) (inhibitor of a caspase-activated deoxyribonuclease) and in the induction of DNA fragmentation. The inhibitory action of selenite on a recombinant active caspase-3 could be reversed by sulfhydryl reducing agents, such as dithiothreitol and β-mercaptoethanol. Furthermore, pretreatment of cells with selenite suppressed the stimulation of the caspase-3-like protease activity in UVB-exposed cells, whereas dithiothreitol and β-mercaptoethanol reversed this suppression of the enzymatic activity. Taken together, our data suggest that selenite inhibits caspase-3-like protease activity through a redox mechanism and that inhibition of caspase-3- like protease activity may be the mechanism by which selenite exerts its protective effect against UVB-induced cell death.

Original languageEnglish (US)
Pages (from-to)8487-8491
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number12
DOIs
StatePublished - Mar 24 2000

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Selenious Acid
Caspase 3
Oxidation-Reduction
Radiation
Peptide Hydrolases
Cell Death
Cell death
Mercaptoethanol
HEK293 Cells
Dithiothreitol
Cells
Caspase Inhibitors
Reducing Agents
Trace Elements
DNA Fragmentation
Selenium
Cell Survival
Chemical activation
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Park, H. S., Huh, S-H., Kim, Y., Shim, J., Lee, S. H., Park, I. S., ... Choi, E. J. (2000). Selenite negatively regulates caspase-3 through a redox mechanism. Journal of Biological Chemistry, 275(12), 8487-8491. https://doi.org/10.1074/jbc.275.12.8487

Selenite negatively regulates caspase-3 through a redox mechanism. / Park, Hee Sae; Huh, Sung-Ho; Kim, Youngho; Shim, Jaekyung; Lee, Seung Hoon; Park, Il Seon; Jung, Yong Keun; Kim, Ick Young; Choi, Eui Ju.

In: Journal of Biological Chemistry, Vol. 275, No. 12, 24.03.2000, p. 8487-8491.

Research output: Contribution to journalArticle

Park, HS, Huh, S-H, Kim, Y, Shim, J, Lee, SH, Park, IS, Jung, YK, Kim, IY & Choi, EJ 2000, 'Selenite negatively regulates caspase-3 through a redox mechanism', Journal of Biological Chemistry, vol. 275, no. 12, pp. 8487-8491. https://doi.org/10.1074/jbc.275.12.8487
Park, Hee Sae ; Huh, Sung-Ho ; Kim, Youngho ; Shim, Jaekyung ; Lee, Seung Hoon ; Park, Il Seon ; Jung, Yong Keun ; Kim, Ick Young ; Choi, Eui Ju. / Selenite negatively regulates caspase-3 through a redox mechanism. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 12. pp. 8487-8491.
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AB - Selenium, an essential biological trace element, exerts its modulatory effects in a variety of cellular events including cell survival and death. In our study we observed that selenite protects HEK293 cells from cell death induced by ultraviolet B radiation (UVB). Exposure of HEK293 cells to UVB radiation resulted in the activation of caspase-3-like protease activity, and pretreatment of the cells with z-DEVD-fmk (N-benzyloxycarbonyl-Asp-Glu-Val- Asp-fluoromethylketone), a caspase-3 inhibitor, prevented UVB-induced cell death. Interestingly, enzymatic activity of caspase-3-like protease in cell lysates of UVB-exposed cells was repressed in vitro by the presence of selenite. Selenite also inhibited the in vitro activity of purified recombinant caspase-3 in cleaving Ac-DEVD-pNA (N-acetyl-Asp-Glu-Asp-p- nitroanilide) or ICAD(L) (inhibitor of a caspase-activated deoxyribonuclease) and in the induction of DNA fragmentation. The inhibitory action of selenite on a recombinant active caspase-3 could be reversed by sulfhydryl reducing agents, such as dithiothreitol and β-mercaptoethanol. Furthermore, pretreatment of cells with selenite suppressed the stimulation of the caspase-3-like protease activity in UVB-exposed cells, whereas dithiothreitol and β-mercaptoethanol reversed this suppression of the enzymatic activity. Taken together, our data suggest that selenite inhibits caspase-3-like protease activity through a redox mechanism and that inhibition of caspase-3- like protease activity may be the mechanism by which selenite exerts its protective effect against UVB-induced cell death.

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