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Superoxide dismutase inactivation in pathophysiology of asthmatic airway remodeling and reactivity.

Authors: Comhair, SA  Xu, W  Ghosh, S  Thunnissen, FB  Almasan, A  Calhoun, WJ  Janocha, AJ  Zheng, L  Hazen, SL  Erzurum, SC 
Citation: Comhair SA, etal., Am J Pathol. 2005 Mar;166(3):663-74.
Pubmed: (View Article at PubMed) PMID:15743779
DOI: Full-text: DOI:10.1016/S0002-9440(10)62288-2

Airway hyperresponsiveness and remodeling are defining features of asthma. We hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a primary event in the pathophysiology of hyperresponsiveness and remodeling that induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to apoptosis were studied in vivo and in vitro. Asthmatic lungs had increased apoptotic epithelial cells compared to controls as determined by terminal dUTP nick-end labeling-positive cells. Apoptosis was confirmed by the finding that caspase-9 and -3 and poly (ADP-ribose) polymerase were cleaved. On the basis that SOD inactivation triggers cell death and low SOD levels occur in asthma, we tested whether SOD inactivation plays a role in airway epithelial cell death. SOD inhibition increased cell death and cleavage/activation of caspases in bronchial epithelial cells in vitro. Furthermore, oxidation and nitration of MnSOD were identified in the asthmatic airway, correlating with physiological parameters of asthma severity. These findings link oxidative and nitrative stress to loss of SOD activity and downstream events that typify asthma, including apoptosis and shedding of the airway epithelium and hyperresponsiveness.

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CRRD Object Information
CRRD ID: 1581231
Created: 2006-09-23
Species: All species
Last Modified: 2006-09-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.