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

doi:10.1111/j.1460-9568.1997.tb00749.x

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

Cancer Biology

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	1831-1837
Number of pages	7
Journal	European Journal of Neuroscience
Volume	9
Issue number	9
DOIs	https://doi.org/10.1111/j.1460-9568.1997.tb00749.x
State	Published - Sep 1997

Keywords

Actinomycin D
GTP cyclohydrolase
Rat
cAMP

ASJC Scopus subject areas

General Neuroscience

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10.1111/j.1460-9568.1997.tb00749.x

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title = "Tetrahydrobiopterin as a mediator of PC12 cell proliferation induced by EGF and NGF",

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.",

keywords = "Actinomycin D, GTP cyclohydrolase, Rat, cAMP",

author = "Anastasiadis, {Panagiotis Z.} and Laurent Bezin and Imerman, {Bruce A.} and Kuhn, {Donald M.} and Louie, {Marisa C.} and Levine, {Robert A.}",

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AU - Anastasiadis, Panagiotis Z.

AU - Bezin, Laurent

AU - Imerman, Bruce A.

AU - Kuhn, Donald M.

AU - Louie, Marisa C.

AU - Levine, Robert A.

PY - 1997/9

Y1 - 1997/9

N2 - 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.

AB - 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.

KW - Actinomycin D

KW - GTP cyclohydrolase

KW - Rat

KW - cAMP

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

Abstract

Keywords

ASJC Scopus subject areas

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