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l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells.

Publication ,  Journal Article
Winnica, D; Que, LG; Baffi, C; Grasemann, H; Fiedler, K; Yang, Z; Etling, E; Wasil, K; Wenzel, SE; Freeman, B; Holguin, F
Published in: Clin Exp Allergy
February 2017

BACKGROUND: Asthma is associated with reduced systemic levels of l-arginine and increased asymmetric dimethylarginine (ADMA). This imbalance leads to nitric oxide synthase (NOS) uncoupling with reduced nitric oxide (NO) formation and greater oxidative and nitrosative stress. Whether this imbalance also occurs in bronchial epitheliumof asthmatics is unknown. OBJECTIVES: We used primary human bronchial epithelial cells (HBECs) from asthmatics and healthy controls to evaluate: (i) ADMA-mediated NOS uncoupling reduces epithelial production of NO and increases oxygen and nitrogen reactive species, and (ii) l-citrulline can reverse this mechanism by recoupling NOS, restoring NO production and reducing oxidative and nitrosative stress. RESULTS: In HBECsIL-13 and INFγ stimulated NOS2 and increased NOx levels. The addition of ADMA reduced NOx and increased H2 O2 levels (p<0.001). Treatment with l-citrulline (800, 1600 μm) rescued NOx when the l-arginine media concentration was 25 μm but failed to do so with higher concentrations (100 μm). Under reduced l-arginine media conditions, HBECs treated with l-citrulline increased the levels of argininosuccinate, an enzyme that metabolizes l-citrulline to l-arginine. l-citrulline prevented the ADMA-mediated increase in nitrotyrosine in HBECs in cells from asthmatics and controls. CONCLUSIONS AND CLINICAL RELEVANCE: Increasing ADMA reduces NO formation and increases oxidative and nitrosative stress in airway epithelial cells. l-citrulline supplementation restores NO formation, while preventing nitrosative stress. These results, suggest that l-citrulline supplementation may indeed be a powerful approach to restore airway NO production and may have a therapeutic potential in diseases in which there is a defective production of NO.

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Published In

Clin Exp Allergy

DOI

EISSN

1365-2222

Publication Date

February 2017

Volume

47

Issue

2

Start / End Page

190 / 199

Location

England

Related Subject Headings

  • Young Adult
  • Respiratory Mucosa
  • Respiratory Function Tests
  • Oxidation-Reduction
  • Nitrosative Stress
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Middle Aged
  • Male
  • Hydrogen Peroxide
 

Citation

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Winnica, D., Que, L. G., Baffi, C., Grasemann, H., Fiedler, K., Yang, Z., … Holguin, F. (2017). l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells. Clin Exp Allergy, 47(2), 190–199. https://doi.org/10.1111/cea.12802
Winnica, D., L. G. Que, C. Baffi, H. Grasemann, K. Fiedler, Z. Yang, E. Etling, et al. “l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells.Clin Exp Allergy 47, no. 2 (February 2017): 190–99. https://doi.org/10.1111/cea.12802.
Winnica D, Que LG, Baffi C, Grasemann H, Fiedler K, Yang Z, et al. l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells. Clin Exp Allergy. 2017 Feb;47(2):190–9.
Winnica, D., et al. “l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells.Clin Exp Allergy, vol. 47, no. 2, Feb. 2017, pp. 190–99. Pubmed, doi:10.1111/cea.12802.
Winnica D, Que LG, Baffi C, Grasemann H, Fiedler K, Yang Z, Etling E, Wasil K, Wenzel SE, Freeman B, Holguin F. l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells. Clin Exp Allergy. 2017 Feb;47(2):190–199.
Journal cover image

Published In

Clin Exp Allergy

DOI

EISSN

1365-2222

Publication Date

February 2017

Volume

47

Issue

2

Start / End Page

190 / 199

Location

England

Related Subject Headings

  • Young Adult
  • Respiratory Mucosa
  • Respiratory Function Tests
  • Oxidation-Reduction
  • Nitrosative Stress
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Middle Aged
  • Male
  • Hydrogen Peroxide