Selective role for superoxide in InsP3 receptor-mediated mitochondrial dysfunction and endothelial apoptosis.
J Cell Biol
; 170(7): 1079-90, 2005 Sep 26.
Article
in En
| MEDLINE
| ID: mdl-16186254
ABSTRACT
Reactive oxygen species (ROS) play a divergent role in both cell survival and cell death during ischemia/reperfusion (I/R) injury and associated inflammation. In this study, ROS generation by activated macrophages evoked an intracellular Ca2+ ([Ca2+]i) transient in endothelial cells that was ablated by a combination of superoxide dismutase and an anion channel blocker. [Ca2+]i store depletion, but not extracellular Ca2+ chelation, prevented [Ca2+]i elevation in response to O2*- that was inositol 1,4,5-trisphosphate (InsP3) dependent, and cells lacking the three InsP3 receptor (InsP3R) isoforms failed to display the [Ca2+]i transient. Importantly, the O2*--triggered Ca2+ mobilization preceded a loss in mitochondrial membrane potential that was independent of other oxidants and mitochondrially derived ROS. Activation of apoptosis occurred selectively in response to O2*- and could be prevented by [Ca2+]i buffering. This study provides evidence that O2*- facilitates an InsP3R-linked apoptotic cascade and may serve a critical function in I/R injury and inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium Channels
/
Apoptosis
/
Receptors, Cytoplasmic and Nuclear
/
Superoxides
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Endothelial Cells
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Mitochondria
Limits:
Animals
Language:
En
Journal:
J Cell Biol
Year:
2005
Document type:
Article
Affiliation country: