Thiol redox disturbances in children with severe asthma are associated with posttranslational modification of the

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Anne M Fitzpatrick1, Susan T Stephenson, Graham R Hadley

  • 1Department of Pediatrics, Emory University, Atlanta, GA, USA. anne.fitzpatrick@emory.edu

The Journal of Allergy and Clinical Immunology
|April 26, 2011
PubMed

Insights

Severe asthma in children involves disrupted thiol redox signaling and impaired nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway function, leading to reduced antioxidant defenses and glutathione depletion.

Area of Science:

  • Pulmonary Medicine
  • Biochemistry
  • Cellular Biology

Background:

  • Airway thiol redox disturbances, particularly glutathione depletion, characterize severe asthma in children.
  • Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is crucial for maintaining antioxidant defense and glutathione homeostasis.

Purpose of the Study:

  • To investigate the expression and activity of Nrf2 and its downstream targets in children with severe asthma.
  • To determine if Nrf2 activation is impaired in severe asthma, leading to thiol depletion and reduced glutathione synthesis.

Main Methods:

  • Collected peripheral blood mononuclear cells (PBMCs) and airway lavage cells from children aged 6-17 with severe and mild-to-moderate asthma.
  • Quantified thiols (glutathione, cysteine) and assessed Nrf2 expression, activity, and downstream targets.

Main Results:

  • Children with severe asthma exhibited increased plasma and airway thiol oxidation and lower glutathione/cysteine levels.
  • Nrf2 mRNA and protein levels were elevated in severe asthma, but the protein was dysfunctional, with no difference in Nrf2 activation or downstream targets between groups.
  • Asthma duration correlated with Nrf2 dysfunction in severe asthma.

Conclusions:

  • Severe asthma in children presents with global thiol redox signaling disruption in airways and circulation, linked to Nrf2 posttranslational modification.
  • The Nrf2 pathway is impaired in severe asthma due to chronic oxidative stress, inhibiting glutathione synthesis and antioxidant defense.
Abstract

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