ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload.
Cell Death Differ
; 13(10): 1675-85, 2006 Oct.
Article
en En
| MEDLINE
| ID: mdl-16410794
ABSTRACT
We set out to identify molecular mechanisms underlying the onset of necrotic Ca(2+) overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca(2+) chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca(2+) was reduced by 60%, thus discarding a role for Ca(2+) channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca(2+) ATPase (PMCA). Remarkably, inhibition of the Na(+)/K(+) ATPase rescued the PMCA and reverted the Ca(2+) rise. Thermodynamic considerations suggest that the Ca(2+) overload develops when the Na(+)/K(+) ATPase, by virtue of the Na(+) overload, clamps the ATP phosphorylation potential below the minimum required by the PMCA. In addition to providing the mechanism for the onset of Ca(2+) overload, the crosstalk between cation pumps offers a novel explanation for the role of Na(+) in cell death.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sodio
/
Adenosina Trifosfato
/
Calcio
/
Proteínas de Transporte de Catión
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Differ
Año:
2006
Tipo del documento:
Article
País de afiliación:
Chile