지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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초록· 키워드
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Deazaadenosine analogs such as 3-deazaadenosine (DZA), 3-deazaaristeromycin (DZAri) and ara-3-deazaadenine (DZAra-A) were developed as inhibitors of S-adenosylhomocysteine (Ado-Hcy) hydrolase (EC 3.3.1.1). These analogs were reported to induce apoptosis in human and murine leukemic cells. But, the mechanism involved in this apoptosis was not clarified yet. In the present study, we analyze the apoptosis induced by deazaadenosine analogs in human cervival cancer cell line, HeLa and the effect of Bcl-2 on this apoptosis. Whereas neither DZAri nor DZAra-A showed inhibitory effect on HeLa cell growth, DZA induced apoptosis in HeLa cells accompanied by cytochrome c release and activation of various caspases such as caspase-2,-8,-9 and -3.0 HeLa-bcl-2 cell line, a stable transfectant of HeLa cell to overexpress Bcl-2, cytochrome c release, activation of all these caspases and the resulted apoptosis by DZA were completely prevented. By in vitro assay of cytochrome c release, in addition, DZA induced cytochrome c release from purified mitochondria of HeLa-pcDNA3 cells, but not HeLa-bcl-2 cells, even in the absence of cytosolic fraction. Therefore, it can be suggested that DZA might damage directly mitochondria leading to activate intrinsic pathway of caspase and thus induce apoptosis. DZA-induced apoptosis in HeLa cells may be in a bel-2-inhibitable manner and irrelative of Ado-Hcy hydrolase.
목차
영어초록
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (21)
참고문헌 신청
[학술지(정기간행물)] - B,Antonsson / 2004 / Mitochondria and the Bcl-2 family proteins in apoptosis signaling pathways / Mol Cell Biochem. 256 : 141 ~ 155
[학술지(정기간행물)] - Y,Akao / 1994 / Multiple subcellular localization of bcl-2: detection in nuclear outer membrane,endoplasmic reticulum membrane, and mitochondrial membranes / Cancer Res. 54 : 2468 ~ 2471
[학술지(정기간행물)] - RR,Aksamit / 1982 / Inhibition of chemotaxis by s-3-deazaadenosylhomocysteine in a mouse macrophage cell line / J Biol Chem. 257 : 621 ~ 625
[학술지(정기간행물)] - PK,Chiang / 1977 / S-Adenosyl-L-homocysteine hydrolase; analogues of S-adenosyl-L-homocysteine as potential inhibitors / Mol Pharmacol. 13 : 939 ~ 947
[학술지(정기간행물)] - PC,Endresen / 1993 / Cell death initiated by 3-deazaadenosine in HL-60 cells is apoptosis and is partially inhibited by homocysteine / Biochem Pharmacol 46 : 1893 ~ 1901
[학술지(정기간행물)] - Y,Akao / 1994 / Multiple subcellular localization of bcl-2: detection in nuclear outer membrane,endoplasmic reticulum membrane, and mitochondrial membranes / Cancer Res. 54 : 2468 ~ 2471
[학술지(정기간행물)] - RR,Aksamit / 1982 / Inhibition of chemotaxis by s-3-deazaadenosylhomocysteine in a mouse macrophage cell line / J Biol Chem. 257 : 621 ~ 625
[학술지(정기간행물)] - PK,Chiang / 1977 / S-Adenosyl-L-homocysteine hydrolase; analogues of S-adenosyl-L-homocysteine as potential inhibitors / Mol Pharmacol. 13 : 939 ~ 947
[학술지(정기간행물)] - PC,Endresen / 1993 / Cell death initiated by 3-deazaadenosine in HL-60 cells is apoptosis and is partially inhibited by homocysteine / Biochem Pharmacol 46 : 1893 ~ 1901
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UCI(KEPA) : I410-ECN-0101-2009-510-017357095