| pubmed-article:12523938 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0521451 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0000098 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0020281 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0085403 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0302583 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:12523938 | lifeskim:mentions | umls-concept:C0079411 | lld:lifeskim |
| pubmed-article:12523938 | pubmed:issue | Pt 1 | lld:pubmed |
| pubmed-article:12523938 | pubmed:dateCreated | 2003-3-20 | lld:pubmed |
| pubmed-article:12523938 | pubmed:abstractText | 1-Methyl-4-phenylpyridinium (MPP(+)) is a neurotoxin used in cellular models of Parkinson's Disease. Although intracellular iron plays a crucial role in MPP(+)-induced apoptosis, the molecular signalling mechanisms linking iron, reactive oxygen species (ROS) and apoptosis are still unknown. We investigated these aspects using cerebellar granule neurons (CGNs) and human SH-SY5Y neuroblastoma cells. MPP(+) enhanced caspase 3 activity after 24 h with significant increases as early as 12 h after treatment of cells. Pre-treatment of CGNs and neuroblastoma cells with the metalloporphyrin antioxidant enzyme mimic, Fe(III)tetrakis(4-benzoic acid)porphyrin (FeTBAP), completely prevented the MPP(+)-induced caspase 3 activity as did overexpression of glutathione peroxidase (GPx1) and pre-treatment with a lipophilic, cell-permeable iron chelator [N, N '-bis-(2-hydroxybenzyl)ethylenediamine-N, N '-diacetic acid, HBED]. MPP(+) treatment increased the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labelling)-positive cells which was completely blocked by pre-treatment with FeTBAP. MPP(+) treatment significantly decreased the aconitase and mitochondrial complex I activities; pre-treatment with FeTBAP, HBED and GPx1 overexpression reversed this effect. MPP(+) treatment increased the intracellular oxidative stress by 2-3-fold, as determined by oxidation of dichlorodihydrofluorescein and dihydroethidium (hydroethidine). These effects were reversed by pre-treatment of cells with FeTBAP and HBED and by GPx1 overexpression. MPP(+)-treatment enhanced the cell-surface transferrin receptor (TfR) expression, suggesting a role for TfR-induced iron uptake in MPP(+) toxicity. Treatment of cells with anti-TfR antibody (IgA class) inhibited MPP(+)-induced caspase activation. Inhibition of nitric oxide synthase activity did not affect caspase 3 activity, apoptotic cell death or ROS generation by MPP(+). Overall, these results suggest that MPP(+)-induced cell death in CGNs and neuroblastoma cells proceeds via apoptosis and involves mitochondrial release of ROS and TfR-dependent iron. | lld:pubmed |
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| pubmed-article:12523938 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12523938 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12523938 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12523938 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12523938 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:12523938 | pubmed:issn | 0264-6021 | lld:pubmed |
| pubmed-article:12523938 | pubmed:author | pubmed-author:KalyanaramanB... | lld:pubmed |
| pubmed-article:12523938 | pubmed:author | pubmed-author:KotamrajuSrig... | lld:pubmed |
| pubmed-article:12523938 | pubmed:author | pubmed-author:KalivendiShas... | lld:pubmed |
| pubmed-article:12523938 | pubmed:author | pubmed-author:HillardCecili... | lld:pubmed |
| pubmed-article:12523938 | pubmed:author | pubmed-author:CunninghamSon... | lld:pubmed |
| pubmed-article:12523938 | pubmed:author | pubmed-author:ShangTiesongT | lld:pubmed |
| pubmed-article:12523938 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12523938 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:12523938 | pubmed:volume | 371 | lld:pubmed |
| pubmed-article:12523938 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12523938 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12523938 | pubmed:pagination | 151-64 | lld:pubmed |
