Document Detail

Dopamine melanin-loaded PC12 cells: a model for studies on pigmented neurons.
MedLine Citation:
PMID:  16029423     Owner:  NLM     Status:  MEDLINE    
The most conspicuous feature in idiopathic parkinsonism is the degeneration of pigmented neurons in the substantia nigra. A major problem for the study of the significance of neuromelanin for the development of parkinsonism is that common experimental animals lack neuromelanin in substantia nigra. The aim of this study was to develop an in vitro model that could be used to study the role of neuromelanin in chemically induced toxicity in dopaminergic cells. Cultured neuron-like PC12 cells were exposed to synthetic dopamine melanin (0-1.0 mg/ml) for 48 h, resulting in uptake of dopamine melanin particles into the cells. The intracellular distribution of dopamine melanin granules was similar to that found in neuromelanin-containing neurons. Dopamine melanin, up to 0.5 mg/ml, had negligible effects on ultrastructure, induction of the endoplasmic reticulum-stress protein glucose regulating protein 78, activation of caspase-3 and cell viability. The decreased cell viability in response to the cytotoxic peptide amyloid-beta25-35 was similar in melanin-loaded cells and in control cells without melanin. The results of the studies suggest that melanin-loaded PC12 cells can serve as an in vitro model for studies on the role of neuromelanin for the toxicity of chemicals, in particular neurotoxicants with melanin affinity, in pigmented neurons.
Anna Ostergren; Anne-Lie Svensson; Nils Gunnar Lindquist; Eva B Brittebo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society     Volume:  18     ISSN:  0893-5785     ISO Abbreviation:  Pigment Cell Res.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-20     Completed Date:  2006-02-03     Revised Date:  2009-10-15    
Medline Journal Info:
Nlm Unique ID:  8800247     Medline TA:  Pigment Cell Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  306-14     Citation Subset:  IM    
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
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MeSH Terms
Amyloid beta-Protein / toxicity
Caspase 3
Caspases / metabolism
Cell Survival / drug effects
Enzyme Activation
Heat-Shock Proteins / biosynthesis
Melanins / metabolism*,  pharmacology
Microscopy, Electron, Transmission
Molecular Chaperones / biosynthesis
Neurons / drug effects,  metabolism*,  ultrastructure
PC12 Cells
Peptide Fragments / toxicity
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Heat-Shock Proteins; 0/Hspa5 protein, rat; 0/Melanins; 0/Molecular Chaperones; 0/Peptide Fragments; 0/amyloid beta-protein (25-35); 0/dopamine melanin; 0/neuromelanin; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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