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Effect of apoptosis-related compounds on Ca2+ transport system in isolated rat liver nuclei

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Abstract

The effect of various inhibitors of DNA topoisomerase II, which has been shown to induce apoptotic cell death, on Ca2+ transport in isolated rat liver nuclei was investigated. Ca2+ uptake and release were determined with a Ca2+ electrode. The presence of aurintricarboxylic acid (ATA; 10-6 to 10-4 M), etoposide (10-4 M), genistein (10-5 and 10-4 M) or amsacrine (10-4 M) in the reaction mixture caused a significant increase in Ca2+ release from the nuclei. Also, these compounds (10-4 M) significantly inhibited Ca2+ uptake by the nuclei. However, the presence of ATA (10-5 and 10-4 M) in the enzyme reaction mixture did not significantly inhibit Ca2+-ATPase activity, which is involved in the nuclear Ca2+ uptake, in the liver nuclei, while etoposide (10-4 M), genistein (10-4 M) and amsacrine (10-4 M) appreciably decreased the enzyme activity. Meanwhile, addition of Ca2+ clearly activated DNA fragmentation in the liver nuclei. The Ca2+ activated DNA fragmentation was significantly prevented by the presence of etoposide, genistein and amsacrine with the concentrations of 10-5 and 10-4 M in the reaction mixture, although ATA (10-5 and 10-4 M) had no effect. The present study demonstrates that some apoptosis inducible compounds used can influence on Ca2+ transport system in isolated rat liver nuclei, suggesting a decrease of nuclear Ca2+ level involved in nuclear functions. (Mol Cell Biochem 166: 183-189, 1997)

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  1. Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka City, 422, Japan

    Sayuri Ueoka & Masayoshi Yamaguchi

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  1. Sayuri Ueoka
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  2. Masayoshi Yamaguchi
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Ueoka, S., Yamaguchi, M. Effect of apoptosis-related compounds on Ca2+ transport system in isolated rat liver nuclei. Mol Cell Biochem 166, 183–189 (1997). https://doi.org/10.1023/A:1006831907937

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