Involvement of Protein Kinase C-Related Anti-apoptosis Signaling in Radiation-Induced Apoptosis in Murine Thymic Lymphoma (3SBH5) Cells

Protein kinase C (PKC; also known as PRKC) is known to be an important participant in radiation-induced apoptosis. However, its role is not fully clarified. Using 3SBH5 cells, which are radiation-sensitive thymic lymphoma cells, the involvement and functions of PKC were assessed in radiation-induced apoptosis. PMA (phorbol 12-myristate 13-acetate), a PKC activator, inhibited the radiation-induced apoptosis in 3SBH5 cells. On the other hand, chelerythrine, a PKC inhibitor, potentiated the apoptosis. In addition, G6976, a classical PKC (cPKC) inhibitor, which specifically inhibits PKC (a and bI ), also promoted the apoptosis. Interestingly, posttreatment (20 min after irradiation) with G6976 had no effect on the radiation-induced apoptosis. These results suggest that cPKC is activated early after irradiation for anti-apoptotic signaling and contributes to the balance between cell survival and death. Indeed, an increase of cPKC activity involving PKC (a, bI and bII) was observed in the cytosolic fraction 3 min after irradiation with 0.5 Gy. However, no translocation of cPKC was observed in the cells after irradiation. Our findings indicate that activation of cPKC (a or b) soon after irradiation is critical to the understanding of the regulation of radiation-induced apoptosis in radiation-sensitive cells