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.

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.

CATALDI, Amelia;DI GIACOMO, Viviana;ZARA, SUSI;RANA, Rosa Alba
2009-01-01

Abstract

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.
File in questo prodotto:
File Dimensione Formato  
1949.pdf

accesso aperto

Tipologia: PDF editoriale
Dimensione 2.52 MB
Formato Adobe PDF
2.52 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/142992
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 22
social impact