Selenite-induced apoptosis of osteoclasts mediated by the mitochondrial pathway.
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.
Chung
Youn Wook
YW
Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul.
Kim
Tae Soo
TS
Lee
Soo Young
SY
Lee
Seoung Hoon
SH
Choi
Yongwon
Y
Kim
Nacksung
N
Min
Byung-Moo
BM
Jeong
Dae-Won
DW
Kim
Ick Young
IY
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
D024101:Mitochondrial Proteins; D013438:Sulfhydryl Compounds; D013481:Superoxides; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D018038:Sodium Selenite