Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma.
BACKGROUND
Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation.


METHODS
To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects.


RESULTS
SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species, reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation.


CONCLUSIONS
These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction.
Comhair
Suzy A A
SA
Department of Pathology, Cleveland Clinic Foundation, OH 44195, USA. comhais@ccf.org
Ricci
Kristin S
KS
Arroliga
Mercedes
M
Lara
Abigail R
AR
Dweik
Raed A
RA
Song
Wei
W
Hazen
Stanley L
SL
Bleecker
Eugene R
ER
Busse
William W
WW
Chung
Kian Fan
KF
Gaston
Benjamin
B
Hastie
Annette
A
Hew
Mark
M
Jarjour
Nizar
N
Moore
Wendy
W
Peters
Stephen
S
Teague
W Gerald
WG
Wenzel
Sally E
SE
Erzurum
Serpil C
SC
D000328:Adult; D000402:Airway Obstruction / Q000201:enzymology; D000596:Amino Acids / Q000097:blood; D001249:Asthma / Q000201:enzymology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D012129:Respiratory Function Tests; D013147:Spirometry; D013482:Superoxide Dismutase / Q000097:blood / Q000172:deficiency*
D000596:Amino Acids; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione