Journal article
Extracellular Signal–Regulated Kinase Activation Delays Hyperoxia-Induced Epithelial Cell Death in Conditions of Akt Downregulation
American journal of respiratory cell and molecular biology, Vol.31(6), pp.611-618
12/2004
DOI: 10.1165/rcmb.2004-0141OC
PMID: 15308507
Abstract
Hyperoxia (fraction of inspired oxygen = 95%) induces death of lung epithelial cells. The duration of cell survival in the setting of hyperoxia depends on hyperoxia-induced activation of intracellular survival pathways. Two survival pathways with known effects on lung epithelial cells are the propidium iodide 3–kinase/Akt and extracellular signal–regulated kinase (ERK)/mitogen-activated protein (MAP) kinase pathways. We investigated the effect of hyperoxia on activity of both the Akt and ERK pathways in the A549 lung epithelial cell line. Hyperoxia-exposed cells show progressive loss of Akt activation and total Akt protein. Hyperoxia decreases Akt mRNA, consistent with the loss of total Akt. In addition, hyperoxia induces ERK activation. Inhibition of ERK with the MAP kinase kinase 1/2 inhibitor, U0126, shortens the survival time of cells in hyperoxia, suggesting that increased ERK activity partially compensates for the hyperoxia-induced Akt downregulation. Our findings show, for the first time, that hyperoxia has divergent effects on two survival pathways (Akt and ERK), and that ERK activity compensates for the loss of the Akt survival effects, delaying the death of hyperoxia-exposed lung epithelial cells.
Details
- Title: Subtitle
- Extracellular Signal–Regulated Kinase Activation Delays Hyperoxia-Induced Epithelial Cell Death in Conditions of Akt Downregulation
- Creators
- Son V. Truong - University of IowaMartha M. Monick - University of IowaTimur O. Yarovinsky - University of IowaLinda S. Powers - University of IowaToru Nyunoya - University of IowaGary W. Hunninghake - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.31(6), pp.611-618
- DOI
- 10.1165/rcmb.2004-0141OC
- PMID
- 15308507
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 12/2004
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984622053902771
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