Suppression of Postmitochondrial Signaling and Delayed Response to UV-induced Nuclear Apoptosis in HeLa Cells.

Accession number;02A0357264
Title;Suppression of Postmitochondrial Signaling and Delayed Response to UV-induced Nuclear Apoptosis in HeLa Cells.
Author; SASAI K (Hiroshima Univ., Hiroshima) YAJIMA H (Hiroshima Univ., Hiroshima) SUZUKI F (Hiroshima Univ., Hiroshima)
Journal Title;Jpn J Cancer Res
Journal Code:F0633A
ISSN:0910-5050
VOL.93;NO.3;PAGE.275-283(2002)
Figure&Table&Reference;FIG.4, REF.36
Pub. Country;Japan
Language;English
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. (author abst.)
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