The role of the presenilin-1 homologue gene sel-12 of Caenorhabditis elegans in apoptotic activities.
J Biol Chem
; 278(14): 12130-4, 2003 Apr 04.
Article
en En
| MEDLINE
| ID: mdl-12556527
ABSTRACT
Many cases of autosomal dominant early onset familial Alzheimer's disease result from mutations in presenilin-1 (PS1). In this study, we examined the role of the PS1 homologue gene sel-12 of Caenorhabditis elegans under oxidative stress and clarified the sel-12-induced apoptosis. A genetic null allele mutant, sel-12(ar171), showed resistance to oxidative stress and prevented mitochondrial dysfunction-induced apoptosis. On the other hand, another allele mutant, sel-12(ar131), that carries a missense mutation showed a proapoptotic activity, which may be the result of a gain of function property. Also, sel-12(ar131)-induced apoptosis was ced-3- and ced-4-dependent. Dantrolene, which specifically inhibits Ca(2+) release from endoplasmic reticulum stores, prevents sel-12(ar131)-induced apoptosis. SEL-12, which is localized in the endoplasmic reticulum, may induce apoptosis through abnormal calcium release from the endoplasmic reticulum. Together, with the previous finding that human PS1 could substitute for SEL-12, these results suggest the similar involvement of PS1-inducing apoptosis under oxidative stress and mitochondrial dysfunction in the Alzheimer's Disease brain.
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Bases de datos:
MEDLINE
Asunto principal:
Proteínas del Helminto
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Caenorhabditis elegans
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Apoptosis
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Proteínas de Caenorhabditis elegans
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Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2003
Tipo del documento:
Article
País de afiliación:
Japón