TY - JOUR
T1 - The protective effect of overexpression of extracellular superoxide dismutase on nitric oxide bioavailability in the lung after exposure to hyperoxia stress
AU - Ahmed, Mohamed N.
AU - Codipilly, Champa
AU - Hogg, Neil
AU - Auten, Richard L.
N1 - Funding Information:
This study was funded in part by a generous donation from the Medical College of Wisconsin Children’s Hospital, Department of Pediatrics, the Children’s Miracle Network, and National Institute of Health R01-GM55792. Address correspondence to Mohamed N. Ahmed, MD, PhD, Neonatal-Perinatal Medicine, North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030, USA. E-mail: [email protected]
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - EC-SOD
KW - NO
KW - cGMP
KW - hyperoxia
KW - oxidative stress
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U2 - 10.3109/01902148.2010.497893
DO - 10.3109/01902148.2010.497893
M3 - Article
C2 - 21077778
AN - SCOPUS:79251487224
SN - 0190-2148
VL - 37
SP - 10
EP - 17
JO - Experimental Lung Research
JF - Experimental Lung Research
IS - 1
ER -