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Functional GPR37 trafficking protects against toxicity induced by 6-OHDA, MPP+ or rotenone in a catecholaminergic cell line.
MedLine Citation:
PMID:  23121049     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
G protein-coupled receptor 37 (GPR37) is suggested to be implicated in the pathogenesis of Parkinson's disease and is accumulating in Lewy bodies within afflicted brain regions. Overexpressed GPR37 is prone to misfolding and aggregation, causing cell death via endoplasmic reticulum stress. While the cytotoxicity of misfolded GPR37 is well established, effects of the functional receptor on cell viability are still unknown. An N2a cell line stably expressing GFP-tagged human GPR37 was created to study its trafficking and effects on cell viability upon challenge with the toxins MPP+, rotenone and 6-OHDA. Neuronal-like differentiation into a tyrosine hydroxylase expressing phenotype, using dibutyryl-cAMP, induced trafficking of GPR37 to the plasma membrane. MTT cell viability and LDH cell death assays revealed that GPR37 was protective against all three toxins in differentiated cells. In undifferentiated cells, the majority of GPR37 was cytoplasmic and the protective effects were more variable: GPR37 expression protected against rotenone and MPP+ but not against 6-OHDA in MTT assays, while it protected against 6-OHDA but not against MPP+ or rotenone in LDH assays. These results suggest that GPR37 functionally trafficked to the plasma membrane protects against toxicity. © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12081.
Authors:
Ebba Gregorsson Lundius; Nikolas Stroth; Vladana Vukojević; Lars Terenius; Per Svenningsson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-1
Journal Detail:
Title:  Journal of neurochemistry     Volume:  -     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12081.
Affiliation:
Laboratory of Translational Neuropharmacology, Karolinska University Hospital Solna, Center for Molecular Medicine / Translational Neuropharmacology, L8:01, 171 64, Solna, Sweden.
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