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Am J Physiol Lung Cell Mol Physiol 277: L787-L793, 1999;
1040-0605/99 $5.00
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Vol. 277, Issue 4, L787-L793, October 1999

Nitric oxide-induced reduction of lung cell and whole lung thioredoxin expression is regulated by NF-kappa B

Jianliang Zhang1, Leonard W. Velsor2, Jawaharlal M. Patel1,3, Edward M. Postlethwait2, and Edward R. Block1,3

1 Department of Medicine, University of Florida, and 3 Research Service, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, Florida 32608; and 2 Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555

We examined whether nitric oxide (NO)-induced inhibition of thioredoxin (Thx) expression is regulated by a mechanism mediated by a transcription factor, i.e., nuclear factor-kappa B (NF-kappa B), in cultured porcine pulmonary artery endothelial cells (PAEC) and in mouse lungs. Western blot analysis revealed that Ikappa B-alpha content was reduced by 20 and 60% in PAEC exposed to 8.5 ppm NO for 2 and 24 h, respectively. NO exposure also caused significant reductions of cytosol fraction p65 and p52 content in PAEC. The nuclear fraction p65 and p52 contents were significantly reduced only in PAEC exposed to NO for 24 h. Exposure to NO resulted in a 50% reduction of p52 mRNA but not of the Ikappa B-alpha subunit. DNA binding activity of the oligonucleotide encoding the NF-kappa B sequence in the Thx gene was significantly reduced in PAEC exposed to NO for 24 h. Exposure of mice to 10 ppm NO for 24 h resulted in a significant reduction of lung Thx and Ikappa B-alpha mRNA and protein expression and in the oligonucleotide encoding Thx and NF-kappa B/DNA binding. These results 1) demonstrate that the effects of NO exposure on Thx expression in PAEC are comparable to those observed in intact lung and 2) suggest that reduced expression of the NF-kappa B subunit, leading to reduced NF-kappa B/DNA binding, is associated with the loss of Thx expression in PAEC and in intact mouse lungs.

nuclear factor-kappa B; transcription factor; gene regulation; mouse lung; lung endothelium


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