Document Detail


Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels.
MedLine Citation:
PMID:  16213988     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, we examined the molecular mechanism by which homocysteine causes neuronal cell apoptosis. We further investigated the mechanisms of melatonin's ability to reduce homocysteine-induced apoptosis. Consistent with its antioxidant properties, melatonin reduced homocysteine-induced lipid peroxidation and stimulated glutathione peroxidase enzyme activity in hippocampus of rats with hyperhomocysteinemia. Furthermore, melatonin treatment diminished cytochrome c release from mitochondria and reduced caspase 3 and caspase 9 activation induced by hyperhomocysteinemia. Chronic hyperhomocysteinemia also led to poly(ADP-ribose) polymerase cleavage and subsequently DNA fragmentation. Treatment with melatonin markedly inhibited poly(ADP-ribose) polymerase cleavage and reduced DNA damage. Hyperhomocysteinemia caused an elevation of pro-apoptotic Bax levels while reducing anti-apoptotic protein, Bcl-2, levels. Daily administration of melatonin up-regulated Bcl-2 and down-regulated Bax levels. We propose that, in addition to its antioxidant properties, melatonin has the ability to protect neuronal cells against apoptosis mediated homocysteine neurotoxicity by modulating apoptosis-regulatory proteins in the hippocampus of rats.
Authors:
G Baydas; R J Reiter; M Akbulut; M Tuzcu; S Tamer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroscience     Volume:  135     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2005  
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-12-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  879-86     Citation Subset:  IM    
Affiliation:
Department of Physiology, Faculty of Medicine, Firat University, Elazig 23119, Turkey. baydas@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Blotting, Western
Caspase 3
Caspases / metabolism*
Cytochromes c / metabolism*
Cytosol / enzymology,  metabolism
DNA Fragmentation
Enzyme Activation / drug effects
Gene Expression Regulation / drug effects
Glutathione Peroxidase / metabolism
Hippocampus / drug effects,  metabolism*
Homocysteine / antagonists & inhibitors*,  toxicity*
Lipid Peroxidation / drug effects
Male
Melatonin / pharmacology*
Mitochondria / enzymology,  metabolism
Neurons / drug effects*
Poly(ADP-ribose) Polymerases / metabolism
Rats
Rats, Wistar
Translocation, Genetic
Chemical
Reg. No./Substance:
454-28-4/Homocysteine; 73-31-4/Melatonin; 9007-43-6/Cytochromes c; EC 1.11.1.9/Glutathione Peroxidase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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


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