| 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. | |
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MedLine Citation:
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PMID: 16213988 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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G Baydas; R J Reiter; M Akbulut; M Tuzcu; S Tamer |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Neuroscience Volume: 135 ISSN: 0306-4522 ISO Abbreviation: Neuroscience Publication Date: 2005 |
Date Detail:
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Created Date: 2005-10-10 Completed Date: 2005-12-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 879-86 Citation Subset: IM |
Affiliation:
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Department of Physiology, Faculty of Medicine, Firat University, Elazig 23119, Turkey. baydas@hotmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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