title: Selenite-induced apoptosis of osteoclasts mediated by the mitochondrial pathway.
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.
authors.affiliation: Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul.
authors.forename: Youn Wook
authors.initials: YW
authors.lastname: Chung
authors.forename: Tae Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Seoung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
authors.forename: Byung-Moo
authors.initials: BM
authors.lastname: Min
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Jeong
authors.forename: Ick Young
authors.initials: IY
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018038:Sodium Selenite / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D013438:Sulfhydryl Compounds; D013481:Superoxides; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D018038:Sodium Selenite