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- Title
Calphostin C-mediated translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction.
- Authors
Ikemoto, H; Tani, E; Ozaki, I; Kitagawa, H; Arita, N
- Abstract
Calphostin C-mediated apoptosis in glioma cells was reported previously to be associated with down-regulation of Bcl-2 and Bcl-x[sub L]. In this study, we report that 100 nM calphostin C also induces translocation and integration of monomeric Bax into mitochondrial membrane, followed by cytochrome c release into cytosol and subsequent decrease of mitochondrial inner membrane potential (ΔΨm) before activation of caspase-3. The integration of monomeric Bax was associated with acquirement of alkali-resistance. The translocated monomeric Bax was partly homodimerized after cytochrome c release and decrease of ΔΨm. The translocation and homodimerization of Bax, cytochrome c release, and decrease of ΔΨm were not blocked by 100 µM z-VAD.fmk, a pan-caspase inhibitor, but the homodimerization of Bax and decrease of ΔΨm were inhibited by 10 µM oligomycin, a mitochondrial F[sub 0]F[sub 1]-ATPase inhibitor. Therefore, it would be assumed that mitochondrial release of cytochrome c results from translocation and integration of Bax and is independent of permeability transition of mitochondria and caspase activation, representing a critical step in calphostin C-induced cell death.
- Subjects
APOPTOSIS; GLIOMAS; MITOCHONDRIA
- Publication
Cell Death & Differentiation, 2000, Vol 7, Issue 6, p511
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4400682