2004年6月
Involvement of ceramide in the mechanism of Cr(VI)-induced apoptosis of CHO cells
FREE RADICAL RESEARCH
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- 巻
- 38
- 号
- 6
- 開始ページ
- 613
- 終了ページ
- 621
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1080/10715760410001694035
- 出版者・発行元
- TAYLOR & FRANCIS LTD
Mitochondria reduce Cr(VI) to Cr(V) with concomitant generation of reactive oxygen species, thereby exhibiting cytotoxic effects leading to apoptosis in various types of cells. To clarify the mechanism by which Cr(VI) induces apoptosis, we examined the effect of Cr(VI) on Chinese hamster ovary (CHO) cells. Cr(VI) increased cellular levels of ceramide by activating acid sphingomyelinase (ASMase) and inhibiting the phosphorylation of pleckstrin homology domain-containing protein kinase B (Akt). Cr(VI) also induced cyclosporin A- and trifluoperazine-sensitive depolarization of mitochondria and activated caspase-3, 8 and 9, thereby causing fragmentation of cellular DNA. The presence of desipramine, an inhibitor of ASMase, and membrane permeable pCPT-cAMP suppressed the Cr(VI)-induced activation of caspases and DNA fragmentation. These results suggested that accumulation of ceramide play an important role in the Cr(VI)-induced apoptosis of CHO cells through activation of mitochondrial membrane permeability transition.
- リンク情報
- ID情報
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- DOI : 10.1080/10715760410001694035
- ISSN : 1071-5762
- Web of Science ID : WOS:000221182200009