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Free Radic Biol Med. 2009 Apr 1;46(7):866-75. doi: 10.1016/j.freeradbiomed.2008.12.001. Epub 2008 Dec 14.

Fatty acid transduction of nitric oxide signaling: nitrolinoleic acid mediates protective effects through regulation of the ERK pathway.

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  • 1Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. kiles@uab.edu

Abstract

In vivo and in vitro studies revealed that nitroalkenes serve as protective mediators in the lung by inducing the cytoprotective enzyme heme oxygenase-1 (HO-1). Nitrolinoleic acid (LNO2) increased HO-1 mRNA, protein, and activity in cultured pulmonary epithelial cells treated with 5 to 50 microM LNO2 and in lungs of rats injected intraperitoneally with 2.6 mg/kg LNO2 twice daily for 20 days. Western blotting revealed that HO-1 protein increased significantly within 4 h of in vitro LNO2 addition and was preceded by an increase in HO-1 mRNA, consistent with transcriptional regulation of HO-1 expression by LNO2. LNO2 also dephosphorylated and activated eukaryotic initiation factor 2alpha, a key translational regulatory protein, indicating that increased translation may also contribute to LNO2-induced increases in HO-1. Exposure of cells to LNO2 activated ERK and JNK, as evidenced by increased phosphorylation. Downstream targets of ERK and JNK, Elk-1 and c-Jun, respectively, were also phosphorylated in response to LNO2 exposure. However, inhibitor studies revealed that only the ERK pathway is necessary for the LNO2-mediated increase in HO-1 mRNA and protein. These data reveal that LNO2 induces pulmonary epithelial HO-1 expression and downstream adaptive responses to inflammation via both transcriptional and translational regulatory mechanisms.

PMID:
19133325
[PubMed - indexed for MEDLINE]
PMCID:
PMC3104854
Free PMC Article

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