Engagement of PI-3-kinase mediated protein kinase C zeta activation in protecting Friend cells from ionizing radiation-induced apoptosis.
Murine erythroleukemia cells (Friend) respond to ionizing radiation with the activation and nuclear translocation of p85alpha subunit of phosphatidylinositol-3-kinase (PI-3-kinase) which mediates the downstream activation and nuclear translocation of atypical Protein kinase C zeta (PKC zeta). This event occurs mainly upon high dose of ionizing radiation (15 Gy) and is concomitant to an increase in BrdU incorporation, which probably accounts for a predominant repair DNA synthesis. Following treatment with wortmannin, a relatively specific inhibitor of PI-3-kinase, both an increased number of apoptotic cells and the inhibition of protein kinase C zeta translocation were detected. Altogether the evidence suggests a potential role of the PI-3-kinase/PKC zeta pathway in protecting Friend cells from ionizing radiation-induced apoptosis offering PKC zeta for consideration as possible target of pharmacological treatments.
Cataldi
Amelia
A
Dipartimento di Biomorfologia, Facoltà di Medicina e Chirurgia, Università G. D'Annunzio, I-66100 Chieti, Italy. cataldi@phobos.unich.it
Di Pietro
Roberta
R
Centurione
Lucia
L
Rapino
Monica
M
Santavenere
Eugenio
E
Garaci
Francesco
F
Cocco
Lucio
L
Giuliani-Piccari
Gabriella
G
Rana
Rosalba
R
D017209:Apoptosis / Q000528:radiation effects*; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D005622:Friend murine leukemia virus; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology / Q000532:radiotherapy*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta