Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells
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 mech...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996106001483 |
| _version_ | 1818734867975766016 |
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| author | Michael Linnebank Holger Lutz Eva Jarre Stefan Vielhaber Carmen Noelker Eduard Struys Cornelis Jakobs Thomas Klockgether Bernd O. Evert Wolfram S. Kunz Ullrich Wüllner |
| author_facet | Michael Linnebank Holger Lutz Eva Jarre Stefan Vielhaber Carmen Noelker Eduard Struys Cornelis Jakobs Thomas Klockgether Bernd O. Evert Wolfram S. Kunz Ullrich Wüllner |
| author_sort | Michael Linnebank |
| collection | DOAJ |
| description | 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 Cu2+, and Cu2+ supplementation prior to HCys treatment preserved COX activity and prevented cell death. The Cu2+ chelating action of HCys and impairement of COX activity represent novel mechanisms of HCys neurotoxicity, which might be preventable by supplementation of Cu2+. |
| first_indexed | 2024-12-18T00:12:11Z |
| format | Article |
| id | doaj.art-bb4256651762400ab38640e85bacee4f |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-18T00:12:11Z |
| publishDate | 2006-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-bb4256651762400ab38640e85bacee4f2022-12-21T21:27:39ZengElsevierNeurobiology of Disease1095-953X2006-09-01233725730Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cellsMichael Linnebank0Holger Lutz1Eva Jarre2Stefan Vielhaber3Carmen Noelker4Eduard Struys5Cornelis Jakobs6Thomas Klockgether7Bernd O. Evert8Wolfram S. Kunz9Ullrich Wüllner10Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, Germany; Corresponding author. Fax: +49 228 287 5024.Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyDepartment of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyDepartment of Neurology, University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, GermanyDepartment of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyDepartment of Clinical Chemistry, Free University Hospital Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsDepartment of Clinical Chemistry, Free University Hospital Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsDepartment of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyDepartment of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyDepartment of Epileptology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyDepartment of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, GermanyChildren 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 Cu2+, and Cu2+ supplementation prior to HCys treatment preserved COX activity and prevented cell death. The Cu2+ chelating action of HCys and impairement of COX activity represent novel mechanisms of HCys neurotoxicity, which might be preventable by supplementation of Cu2+.http://www.sciencedirect.com/science/article/pii/S0969996106001483CopperCOXHomocysteineHomocystinuriaHyperhomocysteinemiaMenkes disease |
| spellingShingle | Michael Linnebank Holger Lutz Eva Jarre Stefan Vielhaber Carmen Noelker Eduard Struys Cornelis Jakobs Thomas Klockgether Bernd O. Evert Wolfram S. Kunz Ullrich Wüllner Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells Neurobiology of Disease Copper COX Homocysteine Homocystinuria Hyperhomocysteinemia Menkes disease |
| title | Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells |
| title_full | Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells |
| title_fullStr | Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells |
| title_full_unstemmed | Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells |
| title_short | Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells |
| title_sort | binding of copper is a mechanism of homocysteine toxicity leading to cox deficiency and apoptosis in primary neurons pc12 and shsy 5y cells |
| topic | Copper COX Homocysteine Homocystinuria Hyperhomocysteinemia Menkes disease |
| url | http://www.sciencedirect.com/science/article/pii/S0969996106001483 |
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