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 apoptosis. In addition, Gö6976, a classical PKC (cPKC) inhibitor, which specifically inhibits PKC (alpha and betaI), also promoted apoptosis. Interestingly, post-treatment (20 min after irradiation) with Gö6976 had no effect on the radiation-induced apoptosis. These results suggest that cPKC is activated early after irradiation for anti-apoptosis signaling and contributes to the balance between cell survival and death. Indeed, an increase of cPKC activity involving PKC (alpha, betaI and betaII) 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 (alpha or beta) soon after irradiation is critical to the understanding of the regulation of radiation-induced apoptosis in radiation-sensitive cells.
Nakajima
Tetsuo
T
Research Center for Radiation Safety, National Institute of Radiological, Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan. otetsu@nirs.go.jp
Yukawa
Osami
O
Azuma
Chihiro
C
Ohyama
Harumi
H
Wang
Bing
B
Kojima
Shuji
S
Hayata
Isamu
I
Hama-Inaba
Hiroko
H
D000470:Alkaloids; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053119:Benzophenanthridines; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D007211:Indoles / Q000494:pharmacology; D008223:Lymphoma / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects; D015398:Signal Transduction / Q000528:radiation effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D002227:Carbazoles; D007211:Indoles; D010617:Phenanthridines; C081021:Go 6976; C016299:chelerythrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate