Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.

Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.
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DOI:
10.1016/j.freeradbiomed.2010.04.020
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发表时间:
2010-07-15
影响因子:
7.4
通讯作者:
Auten, Richard L.
Auten, Richard L.
中科院分区:
医学1区
文献类型:
--
作者:
Brahmajothi, Mulugu V.;Mason, S. Nicholas;Whorton, A. Richard;McMahon, Timothy J.;Auten, Richard L.

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The pathway by which inhaled NO gas enters pulmonary alveolar epithelial cells has not been directly tested. Although the expected mechanism is diffusion, another route is the formation of S-nitroso-L-cysteine, which then enters the cell through the L-type amino acid transporter(LAT). To determine if NO gas also enters alveolar epithelium this way, we exposed alveolar epithelial—rat type I, type II, L2, R3/1, and human A549—cells to NO gas at air liquid interface in the presence of L- and D-cysteine ± LAT competitors. NO gas exposure concentration-dependently increased intracellular NO and S-nitrosothiol levels in the presence of L- but not D-cysteine, which was inhibited by LAT competitors, and was inversely proportional to diffusion distance. The effect of L-cysteine on NO uptake was also concentration dependent. Without pre-incubation with L-cysteine, NO uptake was significantly reduced. We found similar effects using ethyl nitrite gas in place of NO. Exposure to either gas induced activation of soluble guanylyl cylase in a parallel manner, consistent with LAT-dependence. We conclude that NO gas uptake by alveolar epithelium achieves NO-based signaling predominantly by forming extracellular S-nitroso-L-cysteine that is taken up through LAT, rather than by diffusion. Augmenting extracellular S-nitroso-L-cysteine formation may augment pharmacological actions of inhaled NO gas.
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