title: Involvement of caspase-9 in execution of the maternal program of apoptosis in Xenopus late blastulae overexpressed with S-adenosylmethionine decarboxylase.
abstract: 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.
authors.affiliation: Department of Parasitology and Immunology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Takayama
authors.forename: Takayasu
authors.initials: T
authors.lastname: Higo
authors.forename: Masatake
authors.initials: M
authors.lastname: Kai
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukasawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
authors.forename: Takushi
authors.initials: T
authors.lastname: Tadakuma
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yaoita
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shiokawa
mesh_terms: 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*
chemical_list: D011994:Recombinant Proteins; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; D012437:Adenosylmethionine Decarboxylase