NF-kappaB activation plays an antiapoptotic role in human leukemic K562 cells exposed to ionizing radiation.
Exposure of cells to ionizing radiation (IR) determines cellular lesions, such as DNA and membrane damage, which involve a coordinate network of signal transduction pathways responsible for resistance to or delay of apoptosis, depending on cell type and administered dose. Since, after IR exposure, the apoptotic profile appeared different in the two chosen cell lines K562 and Jurkat along with caspase-3 activation, we paid attention to the influence exerted by Protein kinase C delta on transcription factor NF-kappaB activation. Interestingly, K562 resist to IR carrying out a survival strategy which includes PKC delta/NF-kappaB pathway activation, probably mediated by novel IKKs and a role for PI-3-kinase in activating PKC delta at Thr 505 by PDK-1 phosphorylation is suggested. In addition, since caspase-3 is not activated in these cells upon ionizing radiation exposure, it could be supposed that NF-kappaB antagonizes apoptosis induction interfering with pathways which lead to caspase activation, may be by inducing expression of IAP, caspases 3, 7, 9, inhibitor. Thus NF-kappaB activation explains the resistance displayed by K562 to IR and drug potential interference directed to this protein could overcome apoptosis resistance in clinical settings.
Cataldi
Amelia
A
Dipartimento di Biomorfologia, Università G.D'Annunzio, 66100 Chieti, Italy. cataldi@unich.it
Rapino
Monica
M
Centurione
Lucia
L
Sabatini
Nadia
N
Grifone
Giovanna
G
Garaci
Francesco
F
Rana
Rosalba
R
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D003593:Cytoplasm / Q000378:metabolism / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism / Q000528:radiation effects; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells / Q000166:cytology / Q000528:radiation effects; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000528:radiation effects; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism / Q000528:radiation effects; D011839:Radiation, Ionizing
D020672:I-kappa B Proteins; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases