title: Suppression of postmitochondrial signaling and delayed response to UV-induced nuclear apoptosis in HeLa cells.
abstract: Activation of postmitochondrial pathways by UV irradiation was examined using mouse lymphoma 3SB and human leukemic Jurkat cells and two human carcinoma cell lines (HeLa and MCF-7). Exposure of 3SB and Jurkat cells resulted in large amounts of cytochrome c and apoptosis-inducing factor (AIF) being released into the cytosol, and a clear laddering pattern of DNA fragments was observed within 3 h of incubation after irradiation. Simultaneously, activation of caspase-9 and its downstream caspases was detected. HeLa and MCF-7 cells also showed extensive release of mitochondrial factors and caspase-9 activation at 4 to 6 h after exposure, but apoptotic nuclear changes appeared much later. Compared with 3SB and Jurkat cells, these carcinoma cell lines exhibited reduced activation of caspase-9-like proteolytic activity by UV radiation, and levels of caspase-3-like activity in HeLa cells were extremely low, similar to those in caspase-3-deficient MCF-7 cells. These results suggest that the delayed response to UV-induced nuclear apoptosis in HeLa cells is due to a reduced activation of the caspase cascade downstream of cytochrome c release and suppression of caspase-3 activity.
authors.affiliation: Department of Regulatory Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sasai
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Yajima
authors.forename: Fumio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D051033:Apoptosis Inducing Factor; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000528:radiation effects; D003374:Coumarins / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005420:Flavoproteins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014466:Ultraviolet Rays
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D003374:Coumarins; D003574:Cytochrome c Group; D004273:DNA, Neoplasm; D005420:Flavoproteins; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D009842:Oligopeptides; C102580:acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases