Blockage of apoptotic signaling of transforming growth factor-β in human hepatoma cells by carboxyfullerene

被引:75
|
作者
Huang, YL
Shen, CKF
Luh, TY
Yang, HC
Hwang, KC
Chou, CK [1 ]
机构
[1] Vet Gen Hosp, Dept Med Res, Taipei 112, Taiwan
[2] Natl Yang Ming Univ, Inst Biochem, Taipei 112, Taiwan
[3] Natl Taiwan Univ, Dept Chem, Taipei 10764, Taiwan
[4] Natl Tsing Hua Univ, Dept Chem, Hsinchu, Taiwan
[5] Natl Hlth Res Inst, Div Mol & Genom Med, Taipei, Taiwan
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1998年 / 254卷 / 01期
关键词
carboxyfullerene; transforming growth factor-beta; apoptosis; reactive oxygen species;
D O I
10.1046/j.1432-1327.1998.2540038.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transforming growth factor-beta (TGF-beta) has been shown to induce apoptosis in normal hepatocytes and hepatoma cells both in vivo and in vitro. However, the mechanism by which TGF-beta induces apoptosis is not clear. The antiapoptotic activity of antioxidants including N-acetyl-L-cysteine (Ac-Cys), ascorbic acid and a novel free radical scavenger, carboxyfullerene (C-60) on TGF-beta-treated human hepatoma Hep3B cells was examined. Only the water-soluble hexacarboxylic acid derivative of C-60 was found to prevent TGF-beta-induced apoptosis. Antiapoptotic activity of C-60 correlated its ability to eliminate TGF-beta-generated reactive oxygen species (ROSs). However, C-60 did not interfere with TGF-beta-activated PAI-1 promoter activity in the Hep3B cells. These results indicate that the signaling pathway of TGF-beta-induced apoptosis may be related to the generation of ROSs and may be uncoupled from the TGF-beta-activated gene promoter activity. Furthermore, the regioisomer of C-60 with a C-3 symmetry was more potent in protecting cells from apoptosis than that with a D-3 symmetry, and the C-3 isomer had stronger interactions with lipid bilayers than the D-3 isomer. The spectroscopic analysis revealed that the C-3 isomer had stranger interactions with artificial lipid bilayers than the D-3 isomer. Therefore, our study indicates that C-60 may interact with membrane to eliminate TGF-beta-induced ROSs and to prevent apoptosis occur in human hepatoma cells.
引用
收藏
页码:38 / 43
页数:6
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