방사선에 의한 Apoptosis에서 Fas/Fas L의 역할

Abstract

Purpose: The interaction of the Fas: Fas ligand has been recognized to play an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas and Fas ligand mutations, in radiation-induced apoptosis in vivo. Materials and Methods: Mice with a mutation in the Fas (C57BL/6J-Fas(Ipr) and its normal control (C57BL/6J) and the Fas ligand (C3H/HeJ-Fas(gld) and its normal control (C3H/HeJ), were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed at various time intervals, and their spleens collected. Tissue sample was stained with hematoxylin-eosin, and the numbers of apoptotic cells scored. The regulating molecules of apoptosis including the p53, Bcl-2, Bax, Bcl-XL and Bcl-Xs genes were also analyzed by Western blotting. Results: With 2.5 Gy and 10 Gy of irradiation, the levels of apoptosis were lower in C57BL/6J-Fas(Ipr) and C3H/HeJ-Fas(gld) mice than in the control mice(p<0.05). With the expression of apoptosis regulating molecules, the Bax was increased in both the C57BL/6J and C3H/HeJ mice in response to radiation; the peak levels of Bax in the C57BL/6J and C3H/HeJ were 3 and 3.3-fold higher after 8hr, respectively. However the Bax was not increased in either the C57BL/6J-Fas(Ipr) or C3H/HeJ-Fas(gld) mice. The p53, Bcl-XL, Bcl-Xs and Bcl-2 showed no significant changes in the C57BL/6J-Fas(Ipr), C3H/HeJ-Fas(gld), C57BL/6J and C3H/HeJ mice. Conclusion: The levels of radiation-induced apoptosis were lower in the Ipr and gld, than the control mice, which seemed to be related to the level of Bax activation due to the radiation in the Ipr and gld mice. This result suggests that Fas/Fas L plays an important role in radiation-induced apoptosis in vivo.