Selenite-induced apoptosis of osteoclasts mediated by the mitochondrial pathway

Youn Wook Chung, Tae Soo Kim, Soo Young Lee, Seoung Hoon Lee, Yongwon Choi, Nacksung Kim, Byung Moo Min, Dae Won Jeong, Ick Young Kim

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40 Citations (Scopus)

Abstract

The possible effects of sodium selenite on mature osteoclasts were investigated. Incubation of osteoclast-like cells differentiated from RAW 264.7 cells with sodium selenite induced apoptosis as revealed by morphological changes, internucleosomal DNA fragmentation, and activation of caspase-3. Selenite also induced generation of the superoxide anion and reduced the number of free thiol groups in the osteoclast-like cells, suggestive of a shift to a more oxidizing intracellular environment. In addition, selenite induced protein aggregation by thiol cross-linking, loss of the mitochondrial membrane potential, and cytochrome c release in mitochondria isolated from the osteoclast-like cells. Finally, selenite-induced DNA fragmentation in osteoclasts was inhibited both by cyclosporin A, a blocker of the mitochondrial permeability transition pore, and by DEVD-CHO, a cell-permeable inhibitor of caspase-3. These results thus suggest that selenite induces apoptosis mediated by the mitochondrial pathway in mature osteoclasts.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalToxicology Letters
Volume160
Issue number2
DOIs
Publication statusPublished - 2006 Jan 5

Keywords

  • Apoptosis
  • Mitochondria
  • Osteoclast
  • Selenium

ASJC Scopus subject areas

  • Toxicology

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    Chung, Y. W., Kim, T. S., Lee, S. Y., Lee, S. H., Choi, Y., Kim, N., Min, B. M., Jeong, D. W., & Kim, I. Y. (2006). Selenite-induced apoptosis of osteoclasts mediated by the mitochondrial pathway. Toxicology Letters, 160(2), 143-150. https://doi.org/10.1016/j.toxlet.2005.06.019