Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein.
Neurochem Res
; 41(7): 1691-9, 2016 Jul.
Article
em En
| MEDLINE
| ID: mdl-26975317
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.
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Base de dados:
MEDLINE
Assunto principal:
Tirosina 3-Mono-Oxigenase
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Regulação Enzimológica da Expressão Gênica
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Proteínas PrPC
Limite:
Animals
Idioma:
En
Revista:
Neurochem Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Brasil