Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.

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 contributo...

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Autores principales: Joanna A Korecka, Ronald E van Kesteren, Eva Blaas, Sonia O Spitzer, Jorke H Kamstra, August B Smit, Dick F Swaab, Joost Verhaagen, Koen Bossers
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/b9d57f6d28de438980edd24634c769d1
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spelling oai:doaj.org-article:b9d57f6d28de438980edd24634c769d12021-11-18T07:44:10ZPhenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.1932-620310.1371/journal.pone.0063862https://doaj.org/article/b9d57f6d28de438980edd24634c769d12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23724009/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple 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.Joanna A KoreckaRonald E van KesterenEva BlaasSonia O SpitzerJorke H KamstraAugust B SmitDick F SwaabJoost VerhaagenKoen BossersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63862 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Joanna A Korecka
Ronald E van Kesteren
Eva Blaas
Sonia O Spitzer
Jorke H Kamstra
August B Smit
Dick F Swaab
Joost Verhaagen
Koen Bossers
Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
description 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.
format article
author Joanna A Korecka
Ronald E van Kesteren
Eva Blaas
Sonia O Spitzer
Jorke H Kamstra
August B Smit
Dick F Swaab
Joost Verhaagen
Koen Bossers
author_facet Joanna A Korecka
Ronald E van Kesteren
Eva Blaas
Sonia O Spitzer
Jorke H Kamstra
August B Smit
Dick F Swaab
Joost Verhaagen
Koen Bossers
author_sort Joanna A Korecka
title Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
title_short Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
title_full Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
title_fullStr Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
title_full_unstemmed Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling.
title_sort phenotypic characterization of retinoic acid differentiated sh-sy5y cells by transcriptional profiling.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/b9d57f6d28de438980edd24634c769d1
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