Document Detail

The overexpression of copper-zinc superoxide dismutase protects NOS III from nitric oxide-mediated inhibition.
MedLine Citation:
PMID:  12489993     Owner:  NLM     Status:  MEDLINE    
Previously, we have demonstrated that increased superoxide generation plays a role in the nitric oxide (NO)-mediated inhibition of endothelial NO synthase (NOS III) in endothelial cells (ECs). In this study we demonstrate that the source of the superoxide is likely due to both NADPH oxidase and NOS III itself. Further, this increase appears to be linked to the activation of PKC, as PMA could mimic the increase and PKC inhibition ameliorate the increase. To further investigate this phenomenon we determined the effect of overexpression of copper-zinc superoxide dismutase (CuZn-SOD) and Manganese-SOD (Mn-SOD) on the inhibitory effects of NO. Using adenoviral infection we demonstrated that SOD activity was increased and superoxide levels decreased, in both CuZn-SOD and Mn-SOD overexpressing cells compared to cells infected with an adenovirus expressing bacterial beta-galactosidase protein. However, only the CuZn-SOD overexpression reduced the NO-mediated inhibition of NOS III. In addition, the level of NO-induced peroxynitrite generation and nitrated NOS III protein were reduced only in the CuZn-SOD overexpressing cells. In conclusion, our results indicate that superoxide and peroxynitrite are involved in the inhibition of NOS III by NO, and that the scavenging of superoxide may be necessary to prevent NOS III inhibition during treatments that involve inhaled NO or NO donors.
Lisa A Brennan; Stephen Wedgwood; Janine M Bekker; Stephen M Black
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  DNA and cell biology     Volume:  21     ISSN:  1044-5498     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-12-19     Completed Date:  2003-01-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  827-38     Citation Subset:  IM    
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA.
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MeSH Terms
Copper / metabolism
Enzyme Inhibitors / metabolism*
In Situ Nick-End Labeling
Nitric Oxide / metabolism*
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type III
Superoxide Dismutase / metabolism*
Zinc / metabolism
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 7440-50-8/Copper; 7440-66-6/Zinc; EC Oxide Synthase; EC Oxide Synthase Type III; EC Dismutase

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