Published ahead of print on August 12, 2004, doi:10.1165/rcmb.2004-0141OC
Am. J. Respir. Cell Mol. Biol., Volume 31, Number 6, December 2004, 611-618
A more recent version of this article appeared on December 1, 2004
Submitted on April 30, 2004
Revised on August 12, 2004
ERK Activation Delays Hyperoxia-induced Epithelial Cell Death in Conditions of Akt Down Regulation
Son V Truong1, Martha M Monick1*, Timur O Yarovinsky1, Linda S Powers1, Toru Nyunoya1, and Gary W Hunninghake1
1 Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
* To whom correspondence should be addressed. E-mail: martha-monick{at}uiowa.edu.
Hyperoxia (FiO2=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 PI 3-kinase/Akt and ERK 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 MEK1/2 inhibitor, U0126, shortens the survival time of cells in hyperoxia, suggesting that increased ERK activity partially compensates for the hyperoxia-induced Akt down regulation. 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.
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