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Calcium-activated DNA fragmentation in rat liver nuclei
D P Jones1, D J McConkey, P Nicotera
1Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
The Journal of Biological Chemistry
|April 15, 1989
Summary
This study reveals that calcium ions (Ca2+) activate a nuclear endonuclease, leading to DNA fragmentation. This process is linked to programmed cell death (apoptosis) and chemically induced cell killing.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Nuclear DNA hydrolysis is a key event in programmed cell death (apoptosis).
- Calcium ions (Ca2+) are known to play a role in cellular signaling and cell death pathways.
Purpose of the Study:
- To investigate the role of Ca2+ in nuclear DNA fragmentation.
- To identify the molecular mechanisms underlying Ca2+-induced DNA hydrolysis in isolated rat liver nuclei.
Main Methods:
- Incubation of isolated rat liver nuclei with ATP, NAD+, and varying Ca2+ concentrations.
- Measurement of DNA hydrolysis and poly(ADP-ribosyl)ation.
- Assessment of calmodulin-dependent Ca2+ uptake.
Main Results:
- Submicromolar Ca2+ concentrations induced extensive DNA hydrolysis, with half-maximal activity at 200 nM and saturation at 1 microM.
- ATP stimulated a calmodulin-dependent Ca2+ uptake system, mediating endonuclease activation.
- Ca2+-activated DNA fragmentation was inhibited by 3-aminobenzamide and associated with poly(ADP-ribosyl)ation of nuclear proteins.
Conclusions:
- A Ca2+-activated nuclear endonuclease is involved in DNA fragmentation.
- This endonuclease activity may be responsible for DNA fragmentation during apoptosis and chemically induced cell death.