title: Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
abstract: Multiple genetic and environmental factors play a role in the development and progression of Parkinson's disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD.
authors.affiliation: Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. j.korecka@nin.knaw.nl
authors.forename: Joanna A
authors.initials: JA
authors.lastname: Korecka
authors.forename: Ronald E
authors.initials: RE
authors.lastname: van Kesteren
authors.forename: Eva
authors.initials: E
authors.lastname: Blaas
authors.forename: Sonia O
authors.initials: SO
authors.lastname: Spitzer
authors.forename: Jorke H
authors.initials: JH
authors.lastname: Kamstra
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D018377:Neurotransmitter Agents; D050484:Norepinephrine Plasma Membrane Transport Proteins; D014212:Tretinoin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine