Ionizing radiation induces apoptotic signal through protein kinase Cdelta (delta) and survival signal through Akt and cyclic-nucleotide response element-binding protein (CREB) in Jurkat T cells.
Although ionizing radiation induces a loss of proliferative capacity as well as cell death by apoptosis and necrosis, cells can oppose the damaging effects by activating survival signal pathways. Here we report the effect of 1.5- and 6-Gy doses of ionizing radiation on apoptotic protein kinase Cdelta (PKCdelta) and survival cyclic-nucleotide response element-binding protein (CREB) signal in Jurkat T cells. Cell cycle analysis, performed by flow cytometry, showed a significant G2M arrest 24 h after exposure to 6 Gy. This arrest was accompanied by dead cells, which increased in number up to 7 days, when cell viability was further reduced. The response was apparently promoted by caspase-3-mediated PKCdelta activation, and thus apoptosis. Moreover, the presence of viable cells up to 7 days in samples exposed to 6 Gy is explained by Akt activation, which may influence the nuclear transcription factor CREB, leading to resistance to ionizing radiation. Thus, the knowledge of apoptotic and survival pathways activated in tumor cells may help in establishing specific therapies by combining selective inhibitors or stimulators of key signaling proteins with conventional chemotherapy, hormone therapy, and radiotherapy.
Cataldi
Amelia
A
Dipartimento di Biomorfologia, Universitá G. d'Annunzio, Chieti-Pescara, Italy. cataldi@unich.it
Di Giacomo
Viviana
V
Rapino
Monica
M
Zara
Susi
S
Rana
Rosa Alba
RA
D017209:Apoptosis; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011839:Radiation, Ionizing; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000528:radiation effects*
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051745:Protein Kinase C-delta