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Immunosuppressant FK506 Induces Neurite Outgrowth in PC12 Mutant Cells with Impaired NGF-Promoted Neuritogenesis via a Novel MAP Kinase Signaling Pathway

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Abstract

We obtained a drug-hypersensitive PC12 mutant cell (PC12m3), in which neurite outgrowth was strongly stimulated by various drugs such as FK506, calcimycin and cAMP, under the condition of NGF treatment. The frequency of neurite outgrowth stimulated by FK506 was approximately 40 times greater than by NGF alone. The effects of FK506 on neurite outgrowth in PC12m3 cells were inhibited by rapamycin, an FK506 antagonist, and by calcimycin, a calcium ionophore. PC12m3 cells had a strong NGF-induced MAP kinase activity, the same as PC12 parental cells. However, FK506-induced MAP kinase activity was detected only in PC12m3 cells. The activation of MAP kinase by FK506 in PC12m3 cells was markedly inhibited by rapamicin and calcimycin. FK506-induced MAP kinase activity was also inhibited by MAP kinase inhibitor U0126. These results demonstrate that drug-hypersensitive PC12m3 cells have a novel FK506-induced MAP kinase pathway for neuritogenesis.

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Authors and Affiliations

  1. Department of Health Science, Kibi International University, 8 Iga-machi, Takahashi-city, Okayama, 716-8508, Japan

    Yoshio Kano, Fukumi Hiragami, Kenji Kawamura & Michael K. Iwama

  2. Department of Molecular Biology, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701-0192, Japan

    Tsutomu Nohno

  3. Department of Orthopedic Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701-0192, Japan

    Toru Hasegawa

  4. Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan

    Rei Takahashi & Hirotoshi Motoda

  5. Department of Systems Engineering Science, Tokyo Metropolitan Institute of Technology, Asahigaoka 6-6, Hino, Tokyo, 191-0065, Japan

    Kanji Miyamoto

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  1. Yoshio Kano
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Kano, Y., Nohno, T., Hasegawa, T. et al. Immunosuppressant FK506 Induces Neurite Outgrowth in PC12 Mutant Cells with Impaired NGF-Promoted Neuritogenesis via a Novel MAP Kinase Signaling Pathway. Neurochem Res 27, 1655–1661 (2002). https://doi.org/10.1023/A:1021639128120

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