Dysregulated Arginine Metabolism in Young Patients with Chronic Persistent Asthma and in Human Bronchial Epithelial Cells.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI Publishing
    • Subject Terms:
    • Abstract:
      Background: Recent metabolomics studies have found circulatory metabolism alterations in patients with asthma, indicating that altered metabolites played a significant role in asthma. However, the regulatory mechanisms in asthma, especially in young chronic persistent asthma remain underexplored.
      Methods: In this study, a prospective cohort of 162 patients diagnosed of asthma admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to December 2019 was used to perform a nested case-control study. Among them, we included 30 patients with chronic persistent asthma between 20 to 35 years old; 30 health control with evenly distributed age and sex were then recruited. Nontargeted metabolomics was applied to identify serum metabolic profiles and altered metabolic pathways.
      Results: In vitro, human bronchial epithelial cells (HBECs) line BEAS-2B with the addition of L-citrulline and/or asymmetric dimethylarginine (ADMA) model was utilized and the concentrations of nitric oxide (NO) metabolites were tested to evaluate the therapeutic potential of L-citrulline. The young patients with chronic persistent asthma displayed dysregulated serum metabolic profiles, especially enriched in arginine metabolism. The ratio of L-citrulline to ornithine is associated with blood eosinophil count. In vitro, adding L-citrulline could reverse ADMA-mediated reduction of NOx at lower L-arginine concentration (25 μM), but was ineffective in the higher L-arginine concentration (100 μM) media.
      Conclusions: The arginine metabolism balance is of vital importance during the pathogenesis and progression of chronic asthma. L-citrulline could be a powerful approach to restore airway NO production, potentially exhibiting therapeutic benefits among young patients with chronic asthma.
    • References:
      Front Pharmacol. 2021 Mar 23;12:627503. (PMID: 33833679)
      Eur Respir J. 2010 Aug;36(2):269-76. (PMID: 20110397)
      Allergy Asthma Proc. 2014 Sep-Oct;35(5):80-3. (PMID: 25295800)
      Am J Respir Cell Mol Biol. 2013 Jun;48(6):694-702. (PMID: 23470627)
      Nucleic Acids Res. 2010 Jan;38(Database issue):D480-7. (PMID: 19948758)
      J Proteome Res. 2009 Oct;8(10):4844-50. (PMID: 19678709)
      J Asthma Allergy. 2021 Jun 15;14:685-701. (PMID: 34163181)
      Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17017-22. (PMID: 24082129)
      JCI Insight. 2019 Dec 19;4(24):. (PMID: 31714895)
      Anal Chem. 2012 Aug 7;84(15):6619-29. (PMID: 22747237)
      J Allergy Clin Immunol. 2010 Feb;125(2):312-8. (PMID: 20159240)
      Nat Med. 2003 May;9(5):582-8. (PMID: 12669034)
      Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L911-20. (PMID: 19286931)
      Am J Respir Cell Mol Biol. 2007 Jun;36(6):645-53. (PMID: 17218616)
      Basic Clin Pharmacol Toxicol. 2017 Mar;120(3):303-311. (PMID: 27730746)
      Am J Respir Crit Care Med. 2011 Oct 1;184(7):779-85. (PMID: 21719758)
      Spectrochim Acta A Mol Biomol Spectrosc. 2019 Dec 5;223:117318. (PMID: 31272040)
      Thorax. 2004 Sep;59(9):757-60. (PMID: 15333851)
      Cardiovasc Diabetol. 2017 Aug 8;16(1):97. (PMID: 28789650)
      Clin Exp Allergy. 2017 Feb;47(2):190-199. (PMID: 27562295)
      J Allergy Clin Immunol. 2010 Mar;125(3):626-35. (PMID: 20153031)
      Immunol Allergy Clin North Am. 2014 Nov;34(4):767-75. (PMID: 25282289)
      Dis Markers. 2018 Dec 2;2018:5236267. (PMID: 30627225)
      Clin Sci (Lond). 2018 Oct 5;132(19):2135-2146. (PMID: 30190284)
      Nucleic Acids Res. 2014 Jan;42(Database issue):D478-84. (PMID: 24203708)
    • Grant Information:
      81800390 National Natural Science Foundation of China; 2020KW-049, 2021KWZ-25, S2020-YF-GHMS-0014, 2017SF-085, 2020GXLH-Y-015 Key Research and Development Program of Shaanxi; XJTU1AF-CRF-2018-025 the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University
    • Contributed Indexing:
      Keywords: L-citrulline; arginine metabolism; chronic persistent asthma; human airway epithelial cells
    • Accession Number:
      29VT07BGDA (Citrulline)
      31C4KY9ESH (Nitric Oxide)
      63CV1GEK3Y (N,N-dimethylarginine)
      94ZLA3W45F (Arginine)
      E524N2IXA3 (Ornithine)
    • Publication Date:
      Date Created: 20211127 Date Completed: 20211203 Latest Revision: 20211214
    • Publication Date:
      20231215
    • Accession Number:
      PMC8622016
    • Accession Number:
      10.3390/nu13114116
    • Accession Number:
      34836371