Tetrahydrobiopterin as a mediator of PC12 cell proliferation induced by EGF and NGF

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

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Epidermal growth factor and nerve growth factor increased the proliferation of rat phaeochromocytoma PC12 cells through obligatory elevation of intracellular (6R)-tetrahydrobiopterin (BH4). Epidermal growth factor and nerve growth factor increased intracellular BH4 by inducing GTP-cyclohydrolase, the rate-limiting enzyme in BH4 biosynthesis. Specific inhibitors of BH4 biosynthesis prevented growth factor-induced increases in BH4 levels and proliferation. The induction of GTP cyclohydrolase, BH4 and cellular proliferation by nerve growth factor was mediated by cAMP. Elevation of BH4 biosynthesis occurred downstream from cAMP in the cascade used by nerve growth factor to increase proliferation. Thus, intracellular BH4 is an essential mediator of the proliferative effects of epidermal growth factor and nerve growth factor in PC12 cells.

Original languageEnglish (US)
Pages (from-to)1831-1837
Number of pages7
JournalEuropean Journal of Neuroscience
Volume9
Issue number9
DOIs
StatePublished - Sep 1997

Keywords

  • Actinomycin D
  • GTP cyclohydrolase
  • Rat
  • cAMP

ASJC Scopus subject areas

  • Neuroscience(all)

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