Protein kinase C zeta nuclear translocation mediates the occurrence of radioresistance in friend erythroleukemia cells.
Friend erythroleukemia cells require high doses (15 Gy) of ionizing radiation to display a reduced rate of proliferation and an increased number of dead cells. Since ionizing radiation can activate several signaling pathways at the plasma membrane which can lead to the nuclear translocation of a number of proteins, we looked at the intranuclear signaling system activated by Protein Kinases C, being this family of enzymes involved in the regulation of cell growth and death. Our results show an early and dose-dependent increased activity of zeta and epsilon isoforms, although PKC zeta is the only isoform significantly active and translocated into the nuclear compartment upon low (1.5 Gy) and high (15 Gy) radiation doses. These observations are concomitant and consistent with an increase in the anti-apoptotic protein Bcl-2 level upon both radiation doses. Our results point at the involvement of the PKC pathway in the survival response to ionizing radiation of this peculiar cell line, offering PKC zeta for consideration as a possible target of pharmacological treatments aimed at amplifying the effect of such a genotoxic agent.
Cataldi
A
A
Dipartimento di Biomorfologia, Università G. D'Annunzio, Chieti, Italy. cataldi@unich.it
Centurione
L
L
Di Pietro
R
R
Rapino
M
M
Bosco
D
D
Grifone
G
G
Garaci
F
F
Rana
R
R
D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D020287:In Situ Nick-End Labeling; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D011836:Radiation Tolerance; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D020033:Protein Isoforms; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta