| Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells. | |
| | |
MedLine Citation:
|
PMID: 16876425 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Children with hereditary severe hyperhomocysteinemia present with a variety of neurological impairment, and mild hyperhomocysteinemia has been associated with neurodegeneration in the elderly. The link of hyperhomocysteinemia to neurological dysfunction is unknown. We investigated mitochondrial mechanisms of homocysteine (HCys) neurotoxicity in rat dopaminergic pheochromocytoma cells, human neuroblastoma cells and primary rat cerebellar granule neurons. HCys dose dependently impaired cytochrome c oxidase (COX) activity as well as stability and induced reactive oxygen species and apoptotic cell death. We found that HCys binds the COX cofactor Cu(2+), and Cu(2+) supplementation prior to HCys treatment preserved COX activity and prevented cell death. The Cu(2+) chelating action of HCys and impairement of COX activity represent novel mechanisms of HCys neurotoxicity, which might be preventable by supplementation of Cu(2+). |
| | |
Authors:
|
Michael Linnebank; Holger Lutz; Eva Jarre; Stefan Vielhaber; Carmen Noelker; Eduard Struys; Cornelis Jakobs; Thomas Klockgether; Bernd O Evert; Wolfram S Kunz; Ullrich Wüllner |
Related Documents
:
|
20559025 - Cell death when the sac is out of commission. 16969505 - Regulatory roles of cell surface sialylation in sphingolipid-induced cell death in huma... 20353775 - The endocannabinoid system: a new entry in remote cell death mechanisms. 17051335 - Molecular imaging of cell death in vivo by a novel small molecule probe. 16047415 - Extracellular matrix-driven alveolar epithelial cell differentiation in vitro. 19226615 - Characteristic morphology and distribution of bone marrow derived cells in the cornea. |
Publication Detail:
|
Type: Journal Article Date: 2006-07-28 |
Journal Detail:
|
Title: Neurobiology of disease Volume: 23 ISSN: 0969-9961 ISO Abbreviation: Neurobiol. Dis. Publication Date: 2006 Sep |
Date Detail:
|
Created Date: 2006-08-22 Completed Date: 2006-11-01 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9500169 Medline TA: Neurobiol Dis Country: United States |
Other Details:
|
Languages: eng Pagination: 725-30 Citation Subset: IM |
Affiliation:
|
Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, Germany. Michael.Linnebank@ukb.uni-bonn.de |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Animals, Newborn Apoptosis / drug effects, physiology Brain / metabolism*, physiopathology Cells, Cultured Chelating Agents / metabolism, pharmacology Copper / metabolism*, pharmacology Cytochrome-c Oxidase Deficiency / metabolism* Dose-Response Relationship, Drug Electron Transport Complex IV / antagonists & inhibitors, metabolism Homocysteine / metabolism, toxicity Humans Hyperhomocysteinemia / complications, metabolism*, physiopathology Menkes Kinky Hair Syndrome / metabolism, physiopathology Neurodegenerative Diseases / genetics, metabolism*, physiopathology Neurons / drug effects, metabolism*, pathology Neuroprotective Agents / metabolism, pharmacology PC12 Cells Rats |
| Chemical | |
Reg. No./Substance:
|
0/Chelating Agents; 0/Neuroprotective Agents; 454-28-4/Homocysteine; 7440-50-8/Copper; EC 1.9.3.1/Electron Transport Complex IV |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The uncertainties associated with the application of batch technique for distribution coefficients d...
Next Document: Pathologic prion protein is specifically recognized in situ by a novel PrP conformational antibody.