Involvement of ceramide in the mechanism of Cr(VI)-induced apoptosis of CHO cells

Shikibu Muranaka, Tomoko Kanno, Hirofumi Fujita, Hirotsugu Kobuchi, Jitsuo Akiyama, Tatsuji Yasuda, Kozo Utsumi

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)613-621
Number of pages9
JournalFree Radical Research
Volume38
Issue number6
DOIs
Publication statusPublished - Jun 2004

Keywords

  • Apoptosis
  • Ceramide
  • Chromium
  • Mitochondrial permeability transition
  • p-Akt

ASJC Scopus subject areas

  • Biochemistry

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