The protective effect of overexpression of extracellular superoxide dismutase on nitric oxide bioavailability in the lung after exposure to hyperoxia stress. Exp Lung Res 2011 Feb;37(1):10-7
Date
11/17/2010Pubmed ID
21077778DOI
10.3109/01902148.2010.497893Scopus ID
2-s2.0-79251487224 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
The objective of this study was to determine whether overexpression of human extracellular superoxide dismutase (hEC-SOD) can preserve nitric oxide (NO) bioavailability. In vitro studies examined the transient expression of hEC-SOD in mouse epithelial (C10) cells and its effect on extracellular accumulation of NO, intracellular cyclic guanosine monophosphate (cGMP), and nuclear factor kappa B (NF-κB) activation under normal and oxidative stress conditions. In vivo, newborn rabbits were treated with a plasmid containing hEC-SOD cDNA or vehicle plasmid alone, followed by exposure to hyperoxia (Fio₂ = 95% for 7 days). A third group was raised under normoxic conditions. cGMP and NF-κB activation were studied. There was significantly higher NO accumulation in cells expressing hEC-SOD exposed to oxidative stress compared with nontransfected cells. Accumulation of cGMP was significantly higher in cells expressing hEC-SOD. Oxidative stress induced NF-κB activation, which was abrogated by hEC-SOD expression. In vivo, there was significantly higher cGMP accumulation in transfected neonatal rabbit lung tissue at 3 and 7 days of hyperoxic exposure. Immunostaining for NF-κB, showed a marked increase in NF-κB concentration in nontreated neonatal rabbit lung tissue compared to transfected neonatal lung with hEC-SOD and the control air group. These results show that transient EC-SOD overexpression maintains NO bioavailability, which directly leads to maintenance of cGMP activity and reduction of NF-κB activation under oxidative stress.
Author List
Ahmed MN, Codipilly C, Hogg N, Auten RLAuthor
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Biological Availability
Cell Line
Cyclic GMP
Disease Models, Animal
Epithelial Cells
Hyperoxia
Lung
Lung Injury
Mice
NF-kappa B
Nitric Oxide
Oxidative Stress
Rabbits
Superoxide Dismutase
Time Factors
Transfection
Up-Regulation