Human Golgi antiapoptotic protein modulates intracellular calcium fluxes.
Mol Biol Cell
; 20(16): 3638-45, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19553469
ABSTRACT
Golgi antiapoptotic protein (GAAP) is a novel regulator of cell death that is highly conserved in eukaryotes and present in some poxviruses, but its molecular mechanism is unknown. Given that alterations in intracellular Ca(2+) homeostasis play an important role in determining cell sensitivity to apoptosis, we investigated if GAAP affected Ca(2+) signaling. Overexpression of human (h)-GAAP suppressed staurosporine-induced, capacitative Ca(2+) influx from the extracellular space. In addition, it reduced histamine-induced Ca(2+) release from intracellular stores through inositol trisphosphate receptors. h-GAAP not only decreased the magnitude of the histamine-induced Ca(2+) fluxes from stores to cytosol and mitochondrial matrices, but it also reduced the induction and frequency of oscillatory changes in cytosolic Ca(2+). Overexpression of h-GAAP lowered the Ca(2+) content of the intracellular stores and decreased the efficacy of IP(3), providing possible explanations for the observed results. Opposite effects were obtained when h-GAAP was knocked down by siRNA. Thus, our data demonstrate that h-GAAP modulates intracellular Ca(2+) fluxes induced by both physiological and apoptotic stimuli.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Sinalização do Cálcio
/
Proteínas de Membrana
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Biol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Holanda