Calcium-activated DNA fragmentation in rat liver nuclei.
Incubation of isolated rat liver nuclei with ATP, NAD+, and submicromolar Ca2+ concentrations resulted in extensive DNA hydrolysis. Half-maximal activity occurred with 200 nM Ca2+, and saturation of the process was observed with 1 microM Ca2+. ATP stimulated a calmodulin-dependent nuclear Ca2+ uptake system which apparently mediated endonuclease activation. Ca2+-activated DNA fragmentation was inhibited by the inhibitor of poly(ADP-ribose) synthetase, 3-aminobenzamide, and was associated with poly(ADP-ribosyl)ation of nuclear protein. The characteristics of this endonuclease activity indicate that it may be responsible for the Ca2+-dependent fragmentation of DNA involved in programmed cell death (apoptosis) and in certain forms of chemically induced cell killing.
Jones
D P
DP
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
McConkey
D J
DJ
Nicotera
P
P
Orrenius
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002467:Cell Nucleus; D002470:Cell Survival; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004587:Electrophoresis, Agar Gel; D004706:Endodeoxyribonucleases / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000648:ultrastructure; D008970:Molecular Weight; D009243:NAD / Q000494:pharmacology; D051381:Rats
D001549:Benzamides; D007093:Imidazoles; D009243:NAD; C031938:calmidazolium; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D004247:DNA; D004706:Endodeoxyribonucleases; D002118:Calcium