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

doi:10.1016/j.toxlet.2005.06.019

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 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 language	English
Pages (from-to)	143-150
Number of pages	8
Journal	Toxicology Letters
Volume	160
Issue number	2
DOIs	https://doi.org/10.1016/j.toxlet.2005.06.019
Publication status	Published - 2006 Jan 5

Bibliographical note

Funding Information:
This study was supported by a grant (01-PJ5-PG1-01CH12-0002) from the Korea Health 21 R&D Project of the Ministry of Health and Welfare, Republic of Korea (to B.-M.M.), and by a grant (KOSEF 2000-2-20900-008-5) from the Korea Science and Engineering Foundation (to I.Y.K.).

Keywords

Apoptosis
Mitochondria
Osteoclast
Selenium

ASJC Scopus subject areas

Toxicology

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10.1016/j.toxlet.2005.06.019

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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.",

keywords = "Apoptosis, Mitochondria, Osteoclast, Selenium",

author = "Chung, \{Youn Wook\} and Kim, \{Tae Soo\} and Lee, \{Soo Young\} and Lee, \{Seoung Hoon\} and Yongwon Choi and Nacksung Kim and Min, \{Byung Moo\} and Jeong, \{Dae Won\} and Kim, \{Ick Young\}",

note = "Funding Information: This study was supported by a grant (01-PJ5-PG1-01CH12-0002) from the Korea Health 21 R\&D Project of the Ministry of Health and Welfare, Republic of Korea (to B.-M.M.), and by a grant (KOSEF 2000-2-20900-008-5) from the Korea Science and Engineering Foundation (to I.Y.K.). ",

year = "2006",

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doi = "10.1016/j.toxlet.2005.06.019",

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journal = "Toxicology Letters",

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AU - Chung, Youn Wook

AU - Kim, Tae Soo

AU - Lee, Soo Young

AU - Lee, Seoung Hoon

AU - Choi, Yongwon

AU - Kim, Nacksung

AU - Min, Byung Moo

AU - Jeong, Dae Won

AU - Kim, Ick Young

N1 - Funding Information: This study was supported by a grant (01-PJ5-PG1-01CH12-0002) from the Korea Health 21 R&D Project of the Ministry of Health and Welfare, Republic of Korea (to B.-M.M.), and by a grant (KOSEF 2000-2-20900-008-5) from the Korea Science and Engineering Foundation (to I.Y.K.).

PY - 2006/1/5

Y1 - 2006/1/5

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Mitochondria

KW - Osteoclast

KW - Selenium

UR - https://www.scopus.com/pages/publications/27644570063

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DO - 10.1016/j.toxlet.2005.06.019

M3 - Article

C2 - 16111838

AN - SCOPUS:27644570063

SN - 0378-4274

VL - 160

SP - 143

EP - 150

JO - Toxicology Letters

JF - Toxicology Letters

IS - 2

ER -

Selenite-induced apoptosis of osteoclasts mediated by the mitochondrial pathway

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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