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ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload.
- Source :
- Cell Death & Differentiation; Oct2006, Vol. 13 Issue 10, p1675-1685, 11p, 2 Diagrams, 1 Chart, 10 Graphs
- Publication Year :
- 2006
-
Abstract
- We set out to identify molecular mechanisms underlying the onset of necrotic Ca<superscript>2+</superscript> overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca<superscript>2+</superscript> chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca<superscript>2+</superscript> was reduced by 60%, thus discarding a role for Ca<superscript>2+</superscript> channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca<superscript>2+</superscript> ATPase (PMCA). Remarkably, inhibition of the Na<superscript>+</superscript>/K<superscript>+</superscript> ATPase rescued the PMCA and reverted the Ca<superscript>2+</superscript> rise. Thermodynamic considerations suggest that the Ca<superscript>2+</superscript> overload develops when the Na<superscript>+</superscript>/K<superscript>+</superscript> ATPase, by virtue of the Na<superscript>+</superscript> overload, clamps the ATP phosphorylation potential below the minimum required by the PMCA. In addition to providing the mechanism for the onset of Ca<superscript>2+</superscript> overload, the crosstalk between cation pumps offers a novel explanation for the role of Na<superscript>+</superscript> in cell death.Cell Death and Differentiation (2006) 13, 1675–1685. doi:10.1038/sj.cdd.4401852; published online 20 January 2006 [ABSTRACT FROM AUTHOR]
- Subjects :
- SODIUM/POTASSIUM ATPase
ION pumps
EPITHELIAL cells
CELL permeability
CELL death
Subjects
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 13
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 22307729
- Full Text :
- https://doi.org/10.1038/sj.cdd.4401852