Effect of apoptosis-related compounds on Ca2+ transport system in isolated rat liver nuclei.
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.
Ueoka
S
S
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Shizuoka City, Japan.
Yamaguchi
M
M
D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007529:Isoflavones; D000677:Amsacrine; D001312:Aurintricarboxylic Acid; D005047:Etoposide; D019833:Genistein; D002118:Calcium