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J.Health Sci., 49(6), 448-453, 2003

Three-Way Effect of Cyanine Dye on the Structure and Function of Mitochondria

Kikuji Yamashita,a Tomokazu Ichikawa,b, c Takenori Yamamoto,b, c Masatoshi Kataoka,a, b Yoshinori Nakagawa,d Hiroshi Terada,e and Yasuo Shinohara*, b, c, f

aSchool of Dentistry, University of Tokushima, Kuramotocho-3, Tokushima 770-8504, Japan, bInstitute for Genome Research, University of Tokushima, Kuramotocho-3, Tokushima 770-8503, Japan, cFaculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima 770-8505, Japan, dDrugs and Cosmetics Research Center, Hayashibara Biochemical Laboratories, Inc., Shimoishii-1, Okayama 700-0907, Japan, eFaculty of Pharmaceutical Sciences, Tokyo University of Science, Ichigaya, Shinjuku-ku, Tokyo 162-0826, Japan, and fSingle-Molecule Bioanalysis Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Hayashicho 2217 14, Takamatsu 761 0395, Japan

Previously, we found that the cationic cyanine dye tri-S-C4(5) uncoupled mitochondrial oxidative phosphorylation by acting as an inducer of the mitochondrial permeability transition (PT). In the present study, the actions of cyanine dyes such as tri-S-C4(5) and tri-S-C7(5) on the mitochondrial structures and functions were further characterized. In the presence of inorganic phosphate (Pi), cyanine dyes were found to accelerate mitochondrial oxygen consumption that was partially sensitive to the PT inhibitor cyclosporin A (CsA). However, not only the CsA-sensitive but also CsA-insensitive acceleration of mitochondrial respiration was induced by cyanine dyes; and both of them were found to be associated with the release of mitochondrial cytochrome c. On the contrary, in the absence of Pi, moderate acceleration of respiration was induced by cyanine dyes, but this respiratory effect was not associated with the induction of swelling or the release of mitochondrial cytochrome c. Thus, cyanine dyes were concluded to have 3 different effects on the mitochondrial functions depending on the Pi status.