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Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter.

Publication ,  Journal Article
Granillo, OM; Brahmajothi, MV; Li, S; Whorton, AR; Mason, SN; McMahon, TJ; Auten, RL
Published in: Am J Physiol Lung Cell Mol Physiol
July 2008

Nitric oxide (NO) effects are often mediated via S-nitrosothiol (SNO) formation; SNO uptake has recently been shown to be mediated in some cell types via system L-type amino acid transporters (LAT-1, 2). Inhaled NO therapy may exert some biological effects via SNO formation. We therefore sought to determine if pulmonary epithelial SNO uptake depended on LAT or peptide transporter 2 (PEPT2). Both LAT-1 and PEPT2 proteins were detected by immunoblot and immunocytochemistry in L2 cells and rat lung. We tested SNO uptake through the transporters by exposing rat alveolar epithelial cells (L2 and type II) to RSNOs: S-nitrosoglutathione, S-nitrosocysteinylglycine (SNO-Cys-Gly), S-nitrosocysteine (CSNO), and to NO donor diethylamine NONOate (DEA-NONOate). SNO was detected in cell lysates by ozone chemiluminescence. NO uptake was detected by fluorescence in alveolar epithelial cells loaded with 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) diacetate cultured in submersion and exposed to RSNOs and DEA NONOate. Addition of L-Cys but not D-Cys to RSNOs or DEA NONOate increased SNO and DAF-FM signal that was inhibited by coincubation with LAT competitors. Incubation of cells with PEPT2 substrate SNO-Cys-Gly showed no increase in SNO or DAF-FM signal unless incubated with L-Cys. This was unaffected by PEPT2 inhibition. We conclude that RSNOs (thionitrites, S-nitrosothiols) and NO enter alveolar epithelial cells predominantly by S-nitrosation of L-Cys, which is then imported through LAT.

Duke Scholars

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

ISSN

1040-0605

Publication Date

July 2008

Volume

295

Issue

1

Start / End Page

L38 / L43

Location

United States

Related Subject Headings

  • Symporters
  • Respiratory System
  • Rats, Sprague-Dawley
  • Rats
  • Pulmonary Alveoli
  • Nitroso Compounds
  • Nitric Oxide Donors
  • Nitric Oxide
  • Large Neutral Amino Acid-Transporter 1
  • Hydrazines
 

Citation

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MLA
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Granillo, O. M., Brahmajothi, M. V., Li, S., Whorton, A. R., Mason, S. N., McMahon, T. J., & Auten, R. L. (2008). Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter. Am J Physiol Lung Cell Mol Physiol, 295(1), L38–L43. https://doi.org/10.1152/ajplung.00280.2007
Granillo, Olivia M., Mulugu V. Brahmajothi, Sheng Li, A Richard Whorton, S Nicholas Mason, Timothy J. McMahon, and Richard L. Auten. “Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter.Am J Physiol Lung Cell Mol Physiol 295, no. 1 (July 2008): L38–43. https://doi.org/10.1152/ajplung.00280.2007.
Granillo OM, Brahmajothi MV, Li S, Whorton AR, Mason SN, McMahon TJ, et al. Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter. Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L38–43.
Granillo, Olivia M., et al. “Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter.Am J Physiol Lung Cell Mol Physiol, vol. 295, no. 1, July 2008, pp. L38–43. Pubmed, doi:10.1152/ajplung.00280.2007.
Granillo OM, Brahmajothi MV, Li S, Whorton AR, Mason SN, McMahon TJ, Auten RL. Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter. Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L38–L43.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

ISSN

1040-0605

Publication Date

July 2008

Volume

295

Issue

1

Start / End Page

L38 / L43

Location

United States

Related Subject Headings

  • Symporters
  • Respiratory System
  • Rats, Sprague-Dawley
  • Rats
  • Pulmonary Alveoli
  • Nitroso Compounds
  • Nitric Oxide Donors
  • Nitric Oxide
  • Large Neutral Amino Acid-Transporter 1
  • Hydrazines