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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2007.1
- 수록면
- 583 - 593 (11page)
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Heterotrimeric GTP-binding proteins (G proteins) transduce extracellular signals into intracellular sig-nals by activating effector molecules including ad-enylate cyclases that catalyze cAMP formation, and thus regulate various cellular responses such as me-tabolism, proliferation, and apoptosis. cAMP signaling izing radiation-induced apoptosis, but however, the protective mechanism is not clear. Therefore, this study aimed to investigate the signaling molecules and the mechanism mediating the anti-apoptotic action of cAMP signaling system in radiation-induced apopto-sis. Stable expression of a constitutively active mutant of Gαs (GαsQL) protected gamma ray-induced apop-tosis which was asesed by analysis of the cleavages of PARP, caspase-9, and caspase-3 and cytochrome C GαsQL repressed the gamma ray-induced down-regu-lation of Bcl-xL protein, but transfection of Bcl-xL siRNA increased the gamma ray-induced apoptosis and abolished the anti-apoptotic effect of GαsQL. GαsQL decreased the degradation rate of Bcl-xL pro-tein, and it also restrained the decrease in Bcl-xL mRNA by increasing the stability following ionizing irradia-tion. Furthermore, prostaglandin E2 that activates Gαs and the protective effect was abolished by treatment with prostanoid receptor antagonist specific to EP2/4R subtype. Moreover, specific agonists for adenosine A1 receptor that inhibits cAMP signaling pathway aug-mented gamma ray-induced apoptosis. From this study, it is concluded that Gαs-cAMP signaling system can protect SH-SY5Y cells from gamma ray-induced apoptosis partly by restraining down-regulation of Bcl-xL expression, suggesting that radiation-induced apoptosis can be modulated by GPCR ligands to improve
the efficiency of radiation therapy.
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참고문헌 (27)
참고문헌 신청
Ahn YH / 2000 / Protein synthesis-dependent but Bcl-2-independent cytochrome C release in zinc depletion- induced neuronal apoptosis 61 : 508 ~ 514
Boise LH / / a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death : 597 ~ 608
Chin C / 2005 / Radiosensitiza-tion by targeting radioresistance-related genes with protein kinase A inhibitor in radioresistant cancer cells 37 : 608 ~ 618
Cho CH / 2007 / Dibutyryl cAMP stimulates the proliferation of SH-SY5Y human neuroblastoma cells by up-regulating Skp2 protein 133 : 135 ~ 144
Choi SY / 2006 / Activation of Bak and Bax through c-abl-protein kinase Cdelta-p38 MAPK signaling in response to ionizing radiation in human non- small cell lung cancer cells
Boise LH / / a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death : 597 ~ 608
Chin C / 2005 / Radiosensitiza-tion by targeting radioresistance-related genes with protein kinase A inhibitor in radioresistant cancer cells 37 : 608 ~ 618
Cho CH / 2007 / Dibutyryl cAMP stimulates the proliferation of SH-SY5Y human neuroblastoma cells by up-regulating Skp2 protein 133 : 135 ~ 144
Choi SY / 2006 / Activation of Bak and Bax through c-abl-protein kinase Cdelta-p38 MAPK signaling in response to ionizing radiation in human non- small cell lung cancer cells
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