Zusammenfassung
Research on Parkinson's disease (PD) and drug development is hampered by
the lack of suitable human in vitro models that simply and accurately
recreate the disease conditions. To counteract this, many attempts to
differentiate cell lines, such as the human SH-SY5Y neuroblastoma, into
dopaminergic neurons have been undertaken since they are easier to
cultivate when compared with other cellular models. Here, we
characterized neuronal features discriminating undifferentiated and
retinoic acid (RA)-differentiated SH-SYSY cells and described
significant differences between these cell models in 6-hydroxydopamine
(6-OHDA) cytotoxicity. In contrast to undifferentiated cells,
RA-differentiated SH-SY5Y cells demonstrated low proliferative rate and
a pronounced neuronal morphology with high expression of genes related
to synapse vesicle cycle, dopamine synthesis/degradation, and of
dopamine transporter (DAT). Significant differences between
undifferentiated and RA-differentiated SH-SY5Y cells in the overall
capacity of antioxidant defenses were found; although RA-differentiated
SH-SY5Y cells presented a higher basal antioxidant capacity with high
resistance against H2O2 insult, they were twofold more sensitive to
6-OHDA. DAT inhibition by 3 alpha-bis-4-fluorophenyl-methoxytropane and
dithiothreitol (a cell-permeable thiol-reducing agent) protected
RA-differentiated, but not undifferentiated, SH-SY5Y cells from
oxidative damage and cell death caused by 6-OHDA. Here, we demonstrate
that undifferentiated and RA-differentiated SH-SY5Y cells are two unique
phenotypes and also have dissimilar mechanisms in 6-OHDA cytotoxicity.
Hence, our data support the use of RA-differentiated SH-SY5Y cells as an
in vitro model of PD. This study may impact our understanding of the
pathological mechanisms of PD and the development of new therapies and
drugs for the management of the disease.
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