Tetrahydrobiopterin as a Mediator of PC12 Cell Prolifeiation Induced by EGF and NGF
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, th...
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| Published in: | The European journal of neuroscience Vol. 9; no. 9; pp. 1831 - 1837 |
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| Format: | Journal Article |
| Language: | English |
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Blackwell Publishing Ltd
01-09-1997
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| 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. |
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| AbstractList | Epidermal growth factor and nerve growth factor increased the proliferation of rat phaeochromocytoma PC12 cells through obligatory elevation of intracellular (6R)-tetrahydrobiopterin (BH sub(4)). Epidermal growth factor and nerve growth factor increased intracellular BH sub(4) by inducing GTP-cyclohydrolase, the rate-limiting enzyme in BH sub(4) biosynthesis. Specific inhibitors of BH sub(4) biosynthesis prevented growth factor-induced increases in BH sub(4) levels and proliferation. The induction of GTP cyclohydrolase, BH sub(4) and cellular proliferation by nerve growth factor was mediated by CAMP. Elevation of BH sub(4) biosynthesis occurred downstream from CAMP in the cascade used by nerve growth factor to increase proliferation. Thus, intracellular BH sub(4) is an essential mediator of the proliferative effects of epidermal growth factor and nerve growth factor in PC12 cells. 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. Epidermal growth factor and nerve growth factor increased the proliferation of rat phaeochromocytoma PC12 cells through obligatory elevation of intracellular (6R)‐tetrahydrobiopterin (BH 4 ). Epidermal growth factor and nerve growth factor increased intracellular BH 4 by inducing GTP‐cyclohydrolase, the rate‐limiting enzyme in BH 4 biosynthesis. Specific inhibitors of BH 4 biosynthesis prevented growth factor‐induced increases in BH 4 levels and proliferation. The induction of GTP cyclohydrolase, BH 4 and cellular proliferation by nerve growth factor was mediated by CAMP. Elevation of BH 4 biosynthesis occurred downstream from CAMP in the cascade used by nerve growth factor to increase proliferation. Thus, intracellular BH 4 is an essential mediator of the proliferative effects of epidermal growth factor and nerve growth factor in PC12 cells. |
| Author | Kuhn, Donald M. Louie, Marisa C. Bezin, Laurent Imerman, Bruce A. Anastasiadis, Panagiotis Z. Levine, Robert A. |
| Author_xml | – sequence: 1 givenname: Panagiotis Z. surname: Anastasiadis fullname: Anastasiadis, Panagiotis Z. organization: William T. Gossett Neurology Laboratories of Henry Ford Hospital, 1 Ford Place, 4D, Detroit, MI 48202, USA – sequence: 2 givenname: Laurent surname: Bezin fullname: Bezin, Laurent organization: William T. Gossett Neurology Laboratories of Henry Ford Hospital, 1 Ford Place, 4D, Detroit, MI 48202, USA – sequence: 3 givenname: Bruce A. surname: Imerman fullname: Imerman, Bruce A. organization: William T. Gossett Neurology Laboratories of Henry Ford Hospital, 1 Ford Place, 4D, Detroit, MI 48202, USA – sequence: 4 givenname: Donald M. surname: Kuhn fullname: Kuhn, Donald M. organization: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Scott Hall Room 2125, 540 East Canfield, Detroit, MI 48201, USA – sequence: 5 givenname: Marisa C. surname: Louie fullname: Louie, Marisa C. organization: William T. Gossett Neurology Laboratories of Henry Ford Hospital, 1 Ford Place, 4D, Detroit, MI 48202, USA – sequence: 6 givenname: Robert A. surname: Levine fullname: Levine, Robert A. organization: William T. Gossett Neurology Laboratories of Henry Ford Hospital, 1 Ford Place, 4D, Detroit, MI 48202, USA |
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