Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein

Author(s):Show less -

Mello da Luz, Marcio Henrique ^[1] ; Glezer, Isaias ^[1] ; Xavier, Andre Machado ^[1] ; Paiva da Silva, Marcelo Alberti ^[1] ; Monteiro, Jessica ^[1] ; Pino, Volejnik ^[1] ; Zamith, Thiago Panaro ^[1] ; Vieira, Taynara Fernanda ^[1] ; Antonio, Bruno Brito ^[2] ; Moreira Antunes, Hanna Karen ^[3] ; Martins, Vilma Regina ^[4] ; Lee, Kil Sun ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Bioquim, Edificio Pesquisa 2, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Psicobiol, BR-04039032 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Biociencia, BR-04039032 Sao Paulo, SP - Brazil

^[4] AC Camargo Canc Ctr, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Neurochemical Research; v. 41, n. 7, p. 1691-1699, JUL 2016.
• Web of Science Citations: 1

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. (AU)

• FAPESP's process: 13/22413-5 - Alterations of biochemical properties and functions of PrPc induced by endogenous dopamine metabolites and oligomeric amyloid beta peptide
• Grantee: Kil Sun Lee
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC