Document Detail

Unraveling the role of metal ions and low catalytic activity of cytochrome C oxidase in Alzheimer's disease.
MedLine Citation:
PMID:  20725867     Owner:  NLM     Status:  In-Data-Review    
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by high levels of aluminum and certain other metal ions in the brain: The disease is also characterized by low activity of brain cytochrome c oxidase (COX) but whether the elevated metal ions and the low COX activity are linked is not known. Moreover, COX is known to exhibit two catalytic rates (V (max)) and two substrate binding constants (K (m)) but it is not known which of these is affected in AD. In this study, we employed the Klatzo AD rabbit model to evaluate the impact of elevated metal ions on brain COX activity. New Zealand white rabbits were injected intra-cerebrally with 1.4% solutions of either AlCl(3), FeCl(3), CaCl(2), or MgCl(2); and 10 days, later the brain mitochondria were isolated. Polarographic assay revealed that compared to the controls, all four metals led to decreases in the V (max) of the enzyme's low affinity site. The respective decreases were; 16%, 36%, 18%, and 30%. The results suggest a sequence of events in vivo in which oxygen radical damage to mitochondria and COX leads to low ATP production and excess heme establishing conditions thought to be ideal for neurodegeneration.
Trevor Alleyne; Neetu Mohan; Jerome Joseph; Andrew Adogwa
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Publication Detail:
Type:  Journal Article     Date:  2010-08-20
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  43     ISSN:  1559-1166     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  284-9     Citation Subset:  IM    
Department of Preclinical Sciences, Faculty of Medical Sciences, University of the West Indies, St. Augustine, Trinidad and Tobago.
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