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2268903 
Journal Article 
Abstract 
Alteration of nitric oxide synthesis related to abnormal cellular bioenergetics in asthmatic airway epithelium 
Xu, W; Comhair, SAA; Janocha, AJ; Mavrakis, LA; Erzurum, SC 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1436 
English 
WOS:000208771000437 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
In addition to effects on smooth muscle relaxation, nitric oxide (NO) mediates a number of physiologic processes including mitochondrial biogenesis and blockade of cellular respiration. Thus, we hypothesized that the high NO production in asthma might result in greater numbers of mitochondria nonproductive for cellular respiration. To test this, mitochondria ultrastructure in bronchial epithelium, and pyruvate, ATP content, and mitochondria proteins were quantitated in lysates of freshly obtained bronchial epithelial cells from asthmatic and healthy individuals. As previously shown, NO was higher in exhaled breath and inducible NO synthase (iNOS) was higher in airway epithelium of asthmatics as compared to controls; similarly, expression of mitochondrial proteins [Complex III-1 and Complex III-2, arginase II (but not arginase I in the cytosol)] were higher in airway epithelial cells from asthma (n=10) than from healthy controls (n=6) (all P<0.04). Transmission electron microscopy imaging of bronchial biopsies revealed large, light, and dysmorphic mitochondria in asthma as compared to controls. Quantitation revealed increased mitochondria numbers in asthmatic bronchial epithelium as compared to control (P<0.01). Pyruvate, the final product of glycolysis and entry substrate to mitochondrial Krebs cycle that fuels electron transport for ATP production, was higher in asthmatic epithelial cells than controls (P<0.05), yet ATP content in asthmatic epithelial cells was similar to controls (P>0.05). In contrast, lactate, which is formed from pyruvate when cellular respiration is deficient, tended to be higher in bronchoalveolar lavage fluid of asthmatics (P=0.1). Altogether, high levels of iNOS/NO are associated with increased numbers of mitochondria that appear to be less efficient for cellular respiration and ATP production. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010 
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