Properties of DNA fragmentation activity generated by ATP depletion

Citation
N. Nakamura et Y. Wada, Properties of DNA fragmentation activity generated by ATP depletion, CELL DEAT D, 7(5), 2000, pp. 477-484
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL DEATH AND DIFFERENTIATION
ISSN journal
1350-9047 → ACNP
Volume
7
Issue
5
Year of publication
2000
Pages
477 - 484
Database
ISI
SICI code
1350-9047(200005)7:5<477:PODFAG>2.0.ZU;2-3
Abstract
Internucleosomal DNA fragmentation is generally perceived as one of the cha racteristic features of apoptosis, most of which are driven by caspase acti vation dependent upon ATP. On the other hand, ATP depletion has been report ed to induce apoptosis accompanying DNA fragmentation. To address this appa rent paradox, we analyzed the DNA-fragmenting activity generated in ATP-dep leted cells. In HL-60 promyelocytic leukemia cells cultured in glucose-free medium with oligomycin, internucleosomal DNA fragmentation occurred as an early event. The DNA fragmentation was blocked by serine protease inhibitor s but not by caspase inhibitors. Consistently, ICAD/DFF45 could not inhibit the DNA-fragmenting activity of the ATP-depleted cytosol in a cell-free sy stem. When ATP was supplied to the cell-free assay, 80% of the DNA-fragment ing activity was lost. The reduced activity was then restored by proteasome inhibitors, suggesting a role of proteasome to protect from a cellular ins ult derived from ATP-depletion.