期刊
TOXICOLOGY LETTERS
卷 160, 期 2, 页码 143-150出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2005.06.019
关键词
selenium; apoptosis; osteoclast; mitochondria
类别
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 apoprosis mediated by the mitochondrial pathway in mature osteoclasts. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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