EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model
Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamin...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2015/843906 |
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| author | Dan Chen Anumantha G. Kanthasamy Manju B. Reddy |
| author_facet | Dan Chen Anumantha G. Kanthasamy Manju B. Reddy |
| author_sort | Dan Chen |
| collection | DOAJ |
| description | Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05) increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, p<0.01) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001) TH+ cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels. |
| format | Article |
| id | doaj-art-240d970c07064988a1cc9dfe2ba649c4 |
| institution | OA Journals |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-240d970c07064988a1cc9dfe2ba649c42025-08-20T02:04:40ZengWileyParkinson's Disease2090-80832042-00802015-01-01201510.1155/2015/843906843906EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture ModelDan Chen0Anumantha G. Kanthasamy1Manju B. Reddy2Department of Food Sciences and Human Nutrition, Iowa State University, 220 Mackay Hall, Ames, IA 50010, USADepartment of Biomedical Sciences, Iowa State University, Ames, IA 50010, USADepartment of Food Sciences and Human Nutrition, Iowa State University, 220 Mackay Hall, Ames, IA 50010, USABackground. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05) increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, p<0.01) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001) TH+ cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.http://dx.doi.org/10.1155/2015/843906 |
| spellingShingle | Dan Chen Anumantha G. Kanthasamy Manju B. Reddy EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model Parkinson's Disease |
| title | EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model |
| title_full | EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model |
| title_fullStr | EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model |
| title_full_unstemmed | EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model |
| title_short | EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model |
| title_sort | egcg protects against 6 ohda induced neurotoxicity in a cell culture model |
| url | http://dx.doi.org/10.1155/2015/843906 |
| work_keys_str_mv | AT danchen egcgprotectsagainst6ohdainducedneurotoxicityinacellculturemodel AT anumanthagkanthasamy egcgprotectsagainst6ohdainducedneurotoxicityinacellculturemodel AT manjubreddy egcgprotectsagainst6ohdainducedneurotoxicityinacellculturemodel |