Involvement of caspase-9 in execution of the maternal program of apoptosis in Xenopus late blastulae overexpressed with S-adenosylmethionine decarboxylase.
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 [(35)S]procaspase-9, but not [(35)S]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.
Takayama
Eiji
E
Department of Parasitology and Immunology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Higo
Takayasu
T
Kai
Masatake
M
Fukasawa
Masashi
M
Nakajima
Keisuke
K
Hara
Hiroshi
H
Tadakuma
Takushi
T
Igarashi
Kazuei
K
Yaoita
Yoshio
Y
Shiokawa
Koichiro
K
D012437:Adenosylmethionine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D036703:Blastula / Q000166:cytology / Q000502:physiology*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000502:physiology*
D011994:Recombinant Proteins; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; D012437:Adenosylmethionine Decarboxylase