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975874 
Journal Article 
Abstract 
Inhaled nitric oxide prevents the hyperoxia-induced activation of P38 and JNK in neonatal mice lungs 
Stenger, MR; Tile, TE; Rogers, LK; Liu, YS; Nelin, LD 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S117-S117 
English 
WOS:000260867900335 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
Lung growth is a balance between proliferation and cell death. The mitogen-activated protein kinase (MAPK) signal transduction pathway is composed of three major components, extracellular signal-related kinase (ERK), c-JUN amino-terminal kinase (JNK) and p38 MAPK. the MAPK pathways are involved in the cell signaling involved in proliferation via FGF activation of FGFR. Activation of the MAPK pathways has also been implicated in hyperoxic cell death. Thus, both proliferation and cell death in the lung require the MAPK pathways. Reactive nitrogen species have also been implicated in lung injury via activation of the MAPK pathways. We tested the hypothesis that inhaled nitric oxide (NO) affects hyperoxia-induced activation profiles of MAPK pathways in the lung. Neonatal mice were exposed to either room air, >95% O2, or >95% O2 + 10 ppm NO for 72 hours. Protein was harvested from the lungs and immunoblotting for phosphorylated and total ERK, phosphorylated and total p38, and total JNK was carried out. JNK activity was measured in lung protein homogenatesby immune complex kinase assays using [ -32P]ATP and recombinant GST-c-Jun as asubstrate. As expected total levels of ERK, JNK and p38 proteins in the lungs were not affected by 72 hours of oxygen exposures. Exposure to hyperoxia alone resulted in dramatic increase in levels of phosphorylated ERK and p38. Exposure to hyperoxia alone also resulted in a significant increase in JNK activity. the addition of 10 ppm NO to the hyperoxic exposure had little effect on the levels of phosphorylated ERK in the lungs. on the other hand, the 10 ppm NO prevented hyperoxia-induced increase in phosphorylated p38, and the hyperoxia-induced increase in JNK activity in the lung. These results suggest that inhaled NO has important and component specific effects on hyperoxia-induced MAPK activation, and support our hypothesis that inhaled NO affects hyperoxia-induced activation profiles of MAPK pathways in the lung. We speculate that the alterations in MAPK activation profiles may be involved in the mechanisms of NO-mediated affects on hyperoxia-induced lung injury and development. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008