Estrogen-related receptor gamma regulates dopaminergic neuronal phenotype by activating GSK3β/NFAT signaling in SH-SY5Y cells

Journal of Neurochemistry
Juhee LimHyun Jin Choi

Abstract

The orphan nuclear receptor estrogen-related receptor gamma (ERRγ) is highly expressed in the nervous system during embryogenesis and in adult brains, but its physiological role in neuronal development remains unknown. In this study, we evaluated the relevance of ERRγ in regulating dopaminergic (DAergic) phenotype and the corresponding signaling pathway. We used retinoic acid (RA) to differentiate human neuroblastoma SH-SY5Y cells. RA induced neurite outgrowth of SH-SY5Y cells with an increase in DAergic neuron-like properties, including up-regulation of tyrosine hydroxylase, dopamine transporter, and vesicular monoamine transporter 2. ERRγ, but not ERRα, was up-regulated by RA, and participated in RA effect on SH-SY5Y cells. ERRγ over-expression enhanced mature DAergic neuronal phenotype with neurite outgrowth as with RA treatment; and RA-induced increase in DAergic phenotype was attenuated by silencing ERRγ expression. ERRγ appears to have a crucial role in morphological and functional regulation of cells that is selective for DAergic neurons. Polo-like kinase 2 was up-regulated in ERRγ-over-expressing SH-SY5Y cells, which was involved in phosphorylation of glycogen synthase kinase 3β and resulting downstream activation of nu...Continue Reading

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Citations

Jun 27, 2017·Neurobiology of Disease·Rikke H KofoedPoul H Jensen
Jan 13, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hyo In KimHyun Jin Choi
May 29, 2021·Journal of Biochemical and Molecular Toxicology·Yazhi FanHaixiao Feng
Jun 3, 2021·International Journal of Molecular Sciences·Alexander V MaltsevPavel M Balaban

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