Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein

Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein

Author Mello da Luz, Marcio Henrique Autor UNIFESP Google Scholar
Glezer, Isaias Autor UNIFESP Google Scholar
Xavier, Andre Machado Autor UNIFESP Google Scholar
Paiva da Silva, Marcelo Alberti Autor UNIFESP Google Scholar
Monteiro, Jessica Autor UNIFESP Google Scholar
Pino, Volejnik Autor UNIFESP Google Scholar
Zamith, Thiago Panaro Autor UNIFESP Google Scholar
Vieira, Taynara Fernanda Autor UNIFESP Google Scholar
Antonio, Bruno Brito Autor UNIFESP Google Scholar
Moreira Antunes, Hanna Karen Autor UNIFESP Google Scholar
Martins, Vilma Regina Google Scholar
Lee, Kil Sun Autor UNIFESP Google Scholar
Abstract Cellular prion protein (PrPC) is a glycoprotein of the plasma membrane that plays pleiotropic functions by interacting with multiple signaling complexes at the cell surface. Recently, a number of studies have reported the involvement of PrPC in dopamine metabolism and signaling, including its interactions with tyrosine hydroxylase (TH) and dopamine receptors. However, the outcomes reported by independent studies are still debatable. Therefore in this study, we investigated the effects of PrPC on the TH expression during the differentiation of N2a cells with dibutyryl-cAMP, a well-known cAMP analog that activates TH transcription. Upon differentiation, TH was induced with concomitant reduction of PrPC at protein level, but not at mRNA level. shRNA-mediated PrPC reduction increased the basal level of TH at both mRNA and protein levels without dibutyryl-cAMP treatment. This phenotype was reversed by re-expression of PrPC. PrPC knockdown also potentiated the effect of dibutyryl-cAMP on TH expression. Our findings suggest that PrPC has suppressive effects on TH expression. As a consequence, altered PrPC functions may affect the regulation of dopamine metabolism and related neurological disorders.
Keywords Cellular prion protein
Dopamine metabolism
Tyrosine hydroxylase
Gene expression
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
CAPES (Coordenacao de Aperfeicoamento de pessoal de Nivel Superior)
CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
EMU (programa de equipamentos multiusuarios)
Grant number FAPESP: 2013/22413-5
FAPESP: 2013/07937-8
CNPq: 467566/2014-3
Date 2016
Published in Neurochemical Research. New York, v. 41, n. 7, p. 1691-1699, 2016.
ISSN 0364-3190 (Sherpa/Romeo, impact factor)
Publisher Springer/Plenum Publishers
Extent 1691-1699
Access rights Closed access
Type Article
Web of Science ID WOS:000377474000018

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