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S-15176 and its methylated derivative suppress the CsA-insensitive mitochondrial permeability transition and subsequent cytochrome c release induced by silver ion, and show weak protonophoric activity

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Abstract

A recent report has described that S-15176 (N-[(3,5-di-tert-butyl-4-hydroxy-1-thiophenyl)]-3-propyl-N′-(2,3,4-trimethoxybenzyl) piperazine), an anti-ischemic agent, inhibits the mitochondrial permeability transition (PT) induced by not only Ca2+ and inorganic phosphate, but also by tert-butylhydroperoxide or phenylarsine oxide [Morin et al. (Biochem Pharmacol 72:911–918, 2006)]. In the present study, we tested the effects of S-15176 on the PT induced by Ag+, PT of which is not suppressed by cyclosporin A or oligomycin. S-15176 was effective in suppressing the PT and the subsequent cytochrome c release induced by Ag+, and hence, it was concluded to be a more universal PT inhibitor than cyclosporin A or oligomycin. In addition to the PT-suppression activity, S-15176 also showed weak protonophoric activity. Thus, we further tested to investigate whether the hydroxyl group of S-15176 was involved in its PT-suppression or weak protonophoric activities. The methylated derivative of S-15176 also showed both PT suppression and weak protonophoric activities; hence, the hydroxyl group of S-15176 was concluded not to be involved in these activities.

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Abbreviations

CsA:

Cyclosporin A

PT:

Permeability transition

VDAC:

Voltage-dependent anion channel

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Authors and Affiliations

  1. Institute for Genome Research, University of Tokushima, Kuramotocho-3, Tokushima, 770-8503, Japan

    Satoshi Kawashima, Takenori Yamamoto, Yuka Horiuchi, Kengo Fujiwara, Shunichi Gouda, Yuya Yoshimura, Atsushi Yamamoto, Yuki Inotani & Yasuo Shinohara

  2. Graduate School of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima, 770-8505, Japan

    Satoshi Kawashima, Yuka Horiuchi, Kengo Fujiwara, Shunichi Gouda, Yuya Yoshimura, Atsushi Yamamoto, Yuki Inotani, Makoto Kanematsu, Kozo Shishido & Yasuo Shinohara

  3. School of Dentistry, University of Tokushima, Kuramotocho-3, Tokushima, 770-8504, Japan

    Kikuji Yamashita & Seiichiro Kitamura

  4. Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda, 278-8510, Japan

    Hiroshi Terada

Authors
  1. Satoshi Kawashima
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  2. Takenori Yamamoto
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  3. Yuka Horiuchi
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  7. Atsushi Yamamoto
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  9. Kikuji Yamashita
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  11. Hiroshi Terada
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  12. Makoto Kanematsu
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  13. Kozo Shishido
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  14. Yasuo Shinohara
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Corresponding author

Correspondence to Yasuo Shinohara.

Additional information

Satoshi Kawashima, and Takenori Yamamoto contributed equally to this study.

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Kawashima, S., Yamamoto, T., Horiuchi, Y. et al. S-15176 and its methylated derivative suppress the CsA-insensitive mitochondrial permeability transition and subsequent cytochrome c release induced by silver ion, and show weak protonophoric activity. Mol Cell Biochem 358, 45–51 (2011). https://doi.org/10.1007/s11010-011-0919-x

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  • DOI: https://doi.org/10.1007/s11010-011-0919-x

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