Singlet oxygen causes the cytotoxic process of tumour cells in photodynamic therapy. The mechanism by which singlet oxygen damages cells is, however, not fully understood. To address this issue, we synthesized and used two types of endoperoxides, MNPE (1-methylnaphthalene-4-propionate endoperoxide) and NDPE (naphthalene-1,4-dipropionate endoperoxide), that generate defined amounts of singlet oxygen at 37 °C with similar half lives. MNPE, which is more hydrophobic than NDPE, induced the release of cytochrome c from mitochondria into the cytosol and exhibited cytotoxicity, but NDPE did not. RBL cells, a rat basophil leukaemia-derived line, that overexpress phospholipid hydroperoxide glutathione peroxidase in mitochondria were found to be highly resistant to the cytotoxic effect of MNPE. MNPE treatment induced much less DNA ladder formation and nuclear fragmentation in cells than etoposide treatment, even though these treatments induced a similar extent of cellular damage. Singlet oxygen inhibited caspase 9 and 3 activities directly and also suppressed the activation of the caspase cascade. Collectively, these data suggest that singlet oxygen triggers an apoptotic pathway by releasing cytochrome c from mitochondria via the peroxidation of mitochondrial components and results in cell death that is different from typical apoptosis, because of the abortive apoptotic pathway caused by impaired caspase activation.
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Research Article|
June 21 2005
An abortive apoptotic pathway induced by singlet oxygen is due to the suppression of caspase activation
Kaoru OTSU;
Kaoru OTSU
*Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan
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Kazuaki SATO;
Kazuaki SATO
†Department of Chemical Engineering, Faculty of Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa 992-8510, Japan
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Yoshitaka IKEDA;
Yoshitaka IKEDA
‡Division of Molecular Cell Biology, Department of Biomolecular Sciences, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan
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Hirotaka IMAI;
Hirotaka IMAI
§School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
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Yasuhito NAKAGAWA;
Yasuhito NAKAGAWA
§School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
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Yoshihiro OHBA;
Yoshihiro OHBA
†Department of Chemical Engineering, Faculty of Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa 992-8510, Japan
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Junichi FUJII
Junichi FUJII
1
*Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan
1To whom correspondence should be addressed (email jfujii@med.id.yamagata-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
December 13 2004
Revision Received:
March 09 2005
Accepted:
March 16 2005
Accepted Manuscript online:
March 30 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (1): 197–206.
Article history
Received:
December 13 2004
Revision Received:
March 09 2005
Accepted:
March 16 2005
Accepted Manuscript online:
March 30 2005
Citation
Kaoru OTSU, Kazuaki SATO, Yoshitaka IKEDA, Hirotaka IMAI, Yasuhito NAKAGAWA, Yoshihiro OHBA, Junichi FUJII; An abortive apoptotic pathway induced by singlet oxygen is due to the suppression of caspase activation. Biochem J 1 July 2005; 389 (1): 197–206. doi: https://doi.org/10.1042/BJ20042067
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