Induction of apoptosis by depletion of DNA topoisomerase IIα in mammalian cells
| Autor: | Kazuhisa Sekimizu, Shigenobu Tone, Akihiko Kikuchi, Ayako Sakaguchi, Hiroshi Hamamoto, Nobuyoshi Akimitsu, Koushirou Kamura |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Biophysics
Antineoplastic Agents Apoptosis Diketopiperazines Biochemistry Piperazines Mice chemistry.chemical_compound Antigens Neoplasm In Situ Nick-End Labeling medicine Animals Humans Topoisomerase II Inhibitors Benzothiazoles RNA Small Interfering Molecular Biology Mitosis Caspase Fluorescent Dyes Cell Nucleus Mice Knockout biology Nocodazole Cell Biology Transfection Embryo Mammalian Molecular biology Cell biology DNA-Binding Proteins Enzyme Activation Thiazoles Cell nucleus DNA Topoisomerases Type II medicine.anatomical_structure chemistry Caspases biology.protein Topoisomerase-II Inhibitor HeLa Cells Toluene |
| Zdroj: | Biochemical and Biophysical Research Communications. 307:301-307 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/s0006-291x(03)01169-0 |
| Popis: | Inactivation of topoisomerase (topo) IIalpha arrests murine embryonic development. In topo IIalpha-depleted embryos, nuclei were partitioned to daughter cells without complete separation and formed an interconnecting droplet-like structure. The present study examined the fates of topo IIalpha-depleted cells with the droplet-like nuclear structure. When the embryos with abnormal nuclei were further incubated, apoptosis was induced along with the formation of fragmented and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling positive nuclei. ICRF-193 treatment of embryos activated caspases. Apoptosis induced by ICRF-193 was suppressed by z-VAD-fmk, a caspase inhibitor, and pifithrin-alpha, a p53 inhibitor. Moreover, when mitosis was blocked by nocodazole, ICRF-193-induced nuclear abnormalities and apoptosis were abolished. These data suggest that cycling through the M-phase is essential for ICRF-193-induced apoptosis. Nuclear abnormalities similar to those of topo IIalpha-depleted embryos were induced in HeLa cells in which topo IIalpha was knocked down by transfection with short interfering RNA (siRNA) against topo IIalpha, followed by induction of apoptosis. Our results suggest that topo IIalpha-depleted cells with the droplet-like nuclear structure induce apoptosis, which is dependent on caspase and p53 activity during the G1 phase in mammalian cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect