title: Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein.
abstract: Cellular prion protein (PrP(C)) 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 PrP(C) 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 PrP(C) 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 PrP(C) at protein level, but not at mRNA level. shRNA-mediated PrP(C) 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 PrP(C). PrP(C) knockdown also potentiated the effect of dibutyryl-cAMP on TH expression. Our findings suggest that PrP(C) has suppressive effects on TH expression. As a consequence, altered PrP(C) functions may affect the regulation of dopamine metabolism and related neurological disorders.
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Marcio Henrique Mello
authors.initials: MH
authors.lastname: da Luz
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Isaias
authors.initials: I
authors.lastname: Glezer
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Andre Machado
authors.initials: AM
authors.lastname: Xavier
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Marcelo Alberti Paiva
authors.initials: MA
authors.lastname: da Silva
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Jessica Monteiro Volejnik
authors.initials: JM
authors.lastname: Pino
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Thiago Panaro
authors.initials: TP
authors.lastname: Zamith
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil.
authors.forename: Taynara Fernanda
authors.initials: TF
authors.lastname: Vieira
authors.affiliation: Departamento de Psicobiologia, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Bruno Brito
authors.initials: BB
authors.lastname: Antonio
authors.affiliation: Departamento de Biociência, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Hanna Karen Moreira
authors.initials: HK
authors.lastname: Antunes
authors.affiliation: AC Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Vilma Regina
authors.initials: VR
authors.lastname: Martins
authors.affiliation: Departamento de Bioquímica, UNIFESP, Edifício de Pesquisa II, Rua Pedro de Toledo, 669, 8o andar, São Paulo, SP, CEP 04039-032, Brazil. kslee@unifesp.br.
authors.forename: Kil Sun
authors.identifier: http://orcid.org/0000-0002-2390-2774
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D004298:Dopamine / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D018621:PrPC Proteins / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018621:PrPC Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Cellular prion protein; Dopamine metabolism; Gene expression; Tyrosine hydroxylase