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Thiol redox disturbances in children with severe asthma are associated with posttranslational modification of the transcription factor nuclear factor (erythroid-derived 2)–like 2 Anne M. Fitzpatrick, PhD, MSc, Susan T. Stephenson, PhD, Graham R. Hadley, BS, Leandrea Burwell, BS, MPH, Madhuri Penugonda, MD, Dawn M. Simon, MD, Jason Hansen, PhD, Dean P. Jones, PhD, Lou Ann S. Brown, PhD Journal of Allergy and Clinical Immunology Volume 127, Issue 6, Pages (June 2011) DOI: /j.jaci Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 1 Overview of Nrf2 activation and transcription of selected genes related to glutathione (GSH) synthesis and conjugation. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 2 Plasma concentrations of cysteine (Cys; A), glutathione (GSH; B), and the Eh of Cys/cystine (CySS; C) and GSH/GSSG (D) in children with mild-to-moderate asthma (MMA; n = 23) and severe asthma (SA; n = 36). Bar graphs depict the mean ± SEM. Box plots are shown with medians and the upper and lower quartiles in gray. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 3 BAL supernatant concentrations of cysteine (Cys; A), glutathione (GSH; B), and the Eh of Cys/cystine (CySS; C) and GSH/GSSG (D) in children with mild-to-moderate asthma (MMA; n = 18) and severe asthma (SA; n = 23). Bar graphs depict the mean ± SEM. Box plots are shown with medians and the upper and lower quartiles in gray. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 4 Nrf2 and Keap1 mRNA gene expression in PBMCs (A and B) and airway lavage cells (C and D) from children with mild-to-moderate asthma (MMA) and severe asthma (SA). Data were normalized to 5 housekeeping genes and are shown relative to MMA group as 2-ΔΔCT values. Horizontal lines represent the mean. NS, Nonsignificant. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 5 mRNA gene expression of downstream targets of Nrf2 activation responsible for glutathione (GSH) synthesis, including the GST isoenzymes μ, π, and θ (A-C), glutathione synthetase (GSS; D), and glutamate-cysteine ligase (catalytic and modifier subunits; E and F) in PBMCs from children with mild-to-moderate asthma (MMA) and severe asthma (SA). Data were normalized to 5 housekeeping genes and are shown relative to MMA group as 2-ΔΔCT values. Horizontal lines represent the mean. NS, Nonsignificant. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 6 Nrf2 activation (A) and protein expression (B) and Keap1 protein expression (C) in PBMCs from children with mild-to-moderate asthma (MMA) and severe asthma (SA). Nrf2 and Keap1 expression were normalized to β-actin and are expressed relative to the MMA group as mean ± SEM values (Nrf2: MMA, n = 8; SA, n = 16; Keap1: MMA, n = 5; SA, n = 5). Representative images of Nrf2 (D) and Keap1 (E) protein expression. NS, Nonsignificant. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 7 Scatterplot depicting the relationship between Nrf2 mRNA expression in PBMCs and plasma glutathione (GSH; A), the Eh of the GSH:GSSG couple (B), and asthma duration (C). Nrf2 mRNA expression is shown as the fold increase in expression relative to the housekeeping genes. The dashed lines depict the 95% CI. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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