Document Detail


A single-subunit NADH-quinone oxidoreductase renders resistance to mammalian nerve cells against complex I inhibition.
MedLine Citation:
PMID:  12231169     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Numerous studies suggest that dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I) is associated with neurodegenerative disorders, such as Parkinson's disease and Huntington's disease. Development of methods to correct complex I defects seems important. We have previously shown that the single-subunit NADH dehydrogenase of Saccharomyces cerevisiae (Ndi1P) can work as a replacement for complex I in mammalian cells. Using a recombinant adeno-associated virus vector carrying the NDI1 gene, we now demonstrated that the Ndi1 enzyme was successfully expressed in the dopaminergic cell lines rat PC12 and mouse MN9D. The cells expressing the Ndi1 protein were resistant to known inhibitors of complex I, such as rotenone and pyridaben. In addition, the NDI1-transduced cells were still capable of morphological maturation as examined by induction of neurite outgrowth. Also, it was possible to infect the cells after the maturation. The expressed Ndi1 protein was located both in cell bodies and in neurites and was functionally active. It is conceivable that the NDI1 gene will be a promising tool in the treatment of neurodegenerative conditions caused by complex I inhibition.
Authors:
Byoung Boo Seo; Eiko Nakamaru-Ogiso; Terence R Flotte; Takao Yagi; Akemi Matsuno-Yagi
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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:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  6     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-16     Completed Date:  2003-03-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  336-41     Citation Subset:  IM    
Affiliation:
Division of Biochemistry, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Dependovirus / genetics
Electron Transport Complex I
Enzyme Inhibitors / pharmacology
Genetic Vectors
Humans
Mice
NADH, NADPH Oxidoreductases / antagonists & inhibitors,  drug effects,  genetics,  physiology*
Neurites / physiology
Neurons / physiology*
Parkinson Disease / enzymology,  therapy
Rats
Grant Support
ID/Acronym/Agency:
R01DK51809/DK/NIDDK NIH HHS; R01DK53244/DK/NIDDK NIH HHS; R21NS43776/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.5.3/Electron Transport Complex I
Comments/Corrections
Erratum In:
Mol Ther. 2003 Jun;7(6):859

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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