Involvement of caspase-9 in execution of the maternal program of apoptosis in Xenopus late blastulae overexpressed with S-adenosylmethionine decarboxylase

被引:6
作者
Takayama, E
Higo, T
Kai, M
Fukasawa, M
Nakajima, K
Hara, H
Tadakuma, T
Igarashi, K
Yaoita, Y
Shiokawa, K
机构
[1] Natl Def Med Coll, Dept Parasitol & Immunol, Tokorozawa, Saitama 3598513, Japan
[2] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Mol Embryol Lab,Bunkyo Ku, Tokyo 1130033, Japan
[3] Natl Def Med Coll, Dept Microbiol, Tokorozawa, Saitama 3598513, Japan
[4] Tokyo Metropolitan Inst Neurosci, Dept Mol Neurobiol, Fuchu, Tokyo 1838526, Japan
[5] Taisho Pharmaceut Co Ltd, Med Res Labs, Omiya, Saitama 3300031, Japan
[6] Chiba Univ, Grad Sch Pharmaceut Sci, Chuo Ku, Chiba, Japan
关键词
Xenopus laevis embryos; overexpression of SAMDC; maternal program of apoptosis; caspase-9; caspase-1; midblastula transition; RNA microinjection; Bcl-2; peptide inhibitors; dominant-negative caspases;
D O I
10.1016/j.bbrc.2004.10.179
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
We previously demonstrated that overexpression of S-adenosylmethionine decarboxylase (SAMDC) in Xenopus early embryos induces execution of maternal program of apoptosis shortly after midblastula transition, which likely serves as a fail-safe mechanism of early development to eliminate physiologically damaged cells before they entering the gastrula stage. To determine how caspases are involved in this process, we microinjected peptide inhibitors and "dominant-negative forms" of caspase-9 and -1 into Xenopus fertilized eggs, and found that inhibitors of caspase-9, but not caspase-1, completely suppress SAMDC-induced apoptosis. The lysate of SAMDC-overexpressing late blastulae contained activity to cleave in vitro-synthesized [S-35]procaspase-9, but not [S-35]procaspase-1, and mRNA for caspase-9, but not caspase-1, occurred abundantly in the unfertilized egg as maternal mRNA. We also found that overexpression of caspase-9 and -1 equally executes the apoptosis, but the apoptosis executed by these mRNAs was only partially rescued by Bcl-2 and rescued embryos did not develop beyond neurula stage. These results indicate that activation of caspase-9 is a key step for execution of the maternally preset program of apoptosis in Xenopus early embryos. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:1367 / 1375
页数:9
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