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


MeSH Major

  • Apoptosis
  • Carbon Monoxide
  • Caspases
  • Lung
  • Mitogen-Activated Protein Kinases
  • Reperfusion Injury


  • 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.

publication date

  • January 10, 2003



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M208419200

PubMed ID

  • 12399465

Additional Document Info

start page

  • 1248

end page

  • 58


  • 278


  • 2