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

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61 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
Pages (from-to)8487-8491
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number12
DOIs
Publication statusPublished - 2000 Mar 24

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Park, H. S., Huh, S. H., Kim, Y., Shim, J., Lee, S. H., Park, I. S., Jung, Y. K., Kim, I. Y., & 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