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.
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009243:NAD / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D002121:Calcium Channel Blockers; D002147:Calmodulin; D013431:Sulfates; D017967:Zinc Compounds; D009243:NAD; D016718:Arachidonic Acid; D019287:Zinc Sulfate; D004706:Endodeoxyribonucleases; D000252:Calcium-Transporting ATPases; D005033:Ethylmaleimide; D002118:Calcium