Regulation of tyrosine hydroxylase and tetrahydrobiopterin biosynthetic enzymes in PC12 cells by NGF, EGF and IFN-γ

Panagiotis Z. Anastasiadis, Donald M. Kuhn, Jennifer Blitz, Bruce A. Imerman, Marisa C. Louie, Robert A. Levine

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The regulation of catecholamine and tetrahydrobiopterin synthesis was investigated in cultured rat pheochromocytoma PC12 cells following treatments with nerve growth factor (NGF), epidermal growth factor (EGF) and interferon-γ (IFN-γ). NGF and EGF, but not IFN-γ, caused an increase after 24 h in the levels of BH4 and catecholamines, and the activities of tyrosine hydroxylase and GTP cyclohydrolase, the rate-limiting enzymes in catecholamine and BH4 synthesis, respectively. Actinomycin D, a transcriptional inhibitor, blocked treatment-induced elevations in tyrosine hydroxylase and GTP cyclohydrolase activities. NGF, EGF or IFN-γ did not affect the activity of sepiapterin reductase, the final enzyme in BH4 biosynthesis. Rp-cAMP, an inhibitor of cAMP-mediated responses, blocked the induction of tyrosine hydroxylase by NGF or EGF; inhibition of protein kinase C partially blocked the EGF effect, but not the NGF effect. NGF also induced GTP cyclohydrolase in a cAMP-dependent manner, while the EGF effect was not blocked by Rp-cAMP or protein kinase C inhibitors. Sphingosine induced GTP cyclohydrolase in a protein kinase C-independent manner without affecting tyrosine hydroxylase activity. Our results suggest that both tyrosine hydroxylase and GTP cyclohydrolase are induced in a coordinate and transcription-dependent manner by NGF and EGF, while conditions exist where the induction of tyrosine hydroxylase and GTP cyclohydrolase is not coordinately regulated.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalBrain Research
Volume713
Issue number1-2
DOIs
StatePublished - Mar 25 1996

Keywords

  • cyclic adenosine monophosphate
  • epidermal growth factor
  • guanosine triphosphate cyclohydrolase
  • interferon-γ
  • nerve growth factor
  • pheochromocytoma cell
  • sphingosine
  • tetrahydrobiopterin
  • tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Regulation of tyrosine hydroxylase and tetrahydrobiopterin biosynthetic enzymes in PC12 cells by NGF, EGF and IFN-γ'. Together they form a unique fingerprint.

  • Cite this