title: Vitamin D signaling and the differentiation of developing dopamine systems.
abstract: Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover. Our results show that VDR overexpression increases DA neuron differentiation by increasing tyrosine hydroxylase expression, DA production and decreasing the expression of NEUROG2 a marker of immature DA neurons. In the VDR-overexpressing cells, 1,25(OH)2D3 further increased the levels of the DA-metabolites 3-MT and HVA and elevated COMT gene expression. Chromatin immunoprecipitation revealed that 1,25(OH)2D3 increased VDR binding in three regions of the COMT promoter, strongly suggesting direct regulation. In addition, 1,25(OH)2D3 treatment attenuated increased levels of MAOA, DRD2 and VMAT2 gene expression caused by the VDR-overexpression. Taken together, these results show VDR and 1,25(OH)2D3 are directly involved in regulating the expression of dopaminergic-associated genes and that this in vitro neuronal model is a useful tool for identifying the role of 1,25(OH)2D3 in DA neuronal development and maturation.
authors.affiliation: Queensland Brain Institute, University of Queensland, Qld 4072, Australia.
authors.forename: Renata A N
authors.initials: RA
authors.lastname: Pertile
authors.affiliation: Queensland Brain Institute, University of Queensland, Qld 4072, Australia.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Cui
authors.affiliation: Queensland Brain Institute, University of Queensland, Qld 4072, Australia; Queensland Centre for Mental Health Research, Wacol, Qld 4076, Australia. Electronic address: eyles@uq.edu.au.
authors.forename: Darryl W
authors.initials: DW
authors.lastname: Eyles
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D008995:Monoamine Oxidase; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D050493:Vesicular Monoamine Transport Proteins; D014807:Vitamin D; D014815:Vitamins; C581293:DRD2 protein, human; C491183:NEUROG2 protein, human; C493452:SLC18A2 protein, human; C579457:VDR protein, human; C097949:1,25-dihydroxyvitamin D; C579458:monoamine oxidase A, human; C588010:COMT protein, human; C001746:3-methoxytyramine
keywords: COMT; SH-SY5Y; development; dopamine; vitamin D receptor (VDR); vitamin D,1,25(OH)(2)D(3)