Format

Send to

Choose Destination
J Biol Chem. 2003 Jan 10;278(2):1248-58. Epub 2002 Oct 23.

Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3.

Author information

1
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Abstract

Carbon monoxide (CO), a reaction product of the cytoprotective gene heme oxygenase, has been shown to be protective against organ injury in a variety of models. One potential mechanism whereby CO affords cytoprotection is through its anti-apoptotic properties. Our studies show that low level, exogenous CO attenuates anoxia-reoxygenation (A-R)-induced lung endothelial cell apoptosis. Exposure of primary rat pulmonary artery endothelial cells to minimal levels of CO inhibits apoptosis and enhances phospho-p38 mitogen-activated protein kinase (MAPK) activation in A-R. Transfection of p38alpha dominant negative mutant or inhibition of p38 MAPK activity with SB203580 ablates the anti-apoptotic effects of CO in A-R. CO, through p38 MAPK, indirectly modulates caspase 3. Furthermore, we correlate our in vitro apoptosis model with an in vivo model of A-R by showing that CO can attenuate I-R injury of the lung. Taken together, our data are the first to demonstrate in models of A-R that the anti-apoptotic effects of CO are via modulation of p38 MAPK and caspase 3.

PMID:
12399465
DOI:
10.1074/jbc.M208419200
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center