Effect of nuclear Ca2+ uptake inhibitors on Ca(2+)-activated DNA fragmentation in rat liver nuclei

The effect of nuclear Ca2+ uptake inhibitors on the Ca(2+)-activated DNA fragmentation in rat liver nuclei was investigated. The addition of Ca2+ (40 microM) into the reaction mixture containing liver nuclei in the presence of 2.0 mM ATP caused a remarkable increase in nuclear DNA fragmentation. This Ca(2+)-activated DNA fragmentation was not seen in the absence of ATP, because nuclear Ca2+ uptake is not initiated without ATP addition. Moreover, the presence of various reagents (10 microM arachidonic acid, 2.0 mM NAD+, 10 microM zinc sulfate and 0.2 mM N-ethylmaleimide), which could inhibit Ca(2+)-ATPase activity and Ca2+ uptake in the nuclei, produced a significant inhibition of the Ca(2+)-activated DNA fragmentation in the nuclei. The results show that the Ca(2+)-activated DNA fragmentation is involved in the uptake of Ca2+ by the nuclei, suggesting a role of Ca2+ transport system in the regulation of liver nuclear functions.