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    The Ras-ERK pathway is required for the induction of neuronal nitric oxide synthase in differentiating PC12 cells

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    Authors
    Schonhoff, Christopher M.
    Bulseco, Dylan A.
    Brancho, Deborah Marie
    Parada, Luis F.
    Ross, Alonzo H.
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2001-08-03
    Keywords
    Animals; Butadienes; Cell Differentiation; Culture Media, Serum-Free; Enzyme Induction; Enzyme Inhibitors; Flavonoids; Genetic Vectors; Imidazoles; Immunoblotting; Mitogen-Activated Protein Kinases; Nerve Growth Factor; Neurites; Neurons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitriles; PC12 Cells; Pyridines; Rats; ras Proteins
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    https://doi.org/10.1046/j.1471-4159.2001.00432.x
    Abstract
    We have studied the role of MAP kinase pathways in neuronal nitric oxide synthase (nNOS) induction during the differentiation of PC12 cells. In nerve growth factor (NGF)-treated PC12 cells, we find nNOS induced at RNA and protein levels, resulting in increased NOS activity. We note that neither nNOS mRNA, nNOS protein nor NOS activity is induced by NGF treatment in cells that have been infected with a dominant negative Ras adenovirus. We have also used drugs that block MAP kinase pathways and assessed their ability to inhibit nNOS induction. Even though U0126 and PD98059 are both MEK inhibitors, we find that U0126, but not PD98059, blocks induction of nNOS protein and NOS activity in NGF-treated PC12 cells. Also, the p38 kinase inhibitor, SB203580, does not block nNOS induction in our clone of PC12 cells. Since the JNK pathway is not activated in NGF-treated PC12 cells, we conclude that the Ras-ERK pathway and not the p38 or JNK pathway is required for nNOS induction in NGF-treated PC12 cells. We find that U0126 is much more effective than PD98059 in blocking the Ras-ERK pathway, thereby explaining the discrepancy in nNOS inhibition. We conclude that the Ras-ERK pathway is required for nNOS induction.
    Source

    J Neurochem. 2001 Aug;78(3):631-9.

    DOI
    10.1046/j.1471-4159.2001.00432.x
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32514
    PubMed ID
    11483666
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1046/j.1471-4159.2001.00432.x
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