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Inhibition of the proliferation of cultured immortalized schwann cells by forskolin with a decreased basal level of diacylglycerol

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Abstract

The repetitive passages of a Schwann cell culture results in the appearance of immortalized cells. In order to investigate the direct effects of cyclic AMP (cAMP) on Schwann cell proliferation, we used the immortalized Schwann cells because the responses of a short-term Schwann cell culture to agents increasing the intracellular cAMP are more complicated and it does not seem that all of them are due to the direct effects of cAMP. By adding up to 200 μM of forskolin, an adenylate cyclase activator, to the culture medium, Schwann cell proliferation was inhibited and the intracellular 1,2-diacylglycerol (DG) level was decreased in a dose-dependent manner to 44 and 53% of the control values, respectively. The protein phosphorylation activity in the cytosol from the cell treated with 100 μM forskolin, assayed with myelin basic protein as the acceptor, decreased to 78% and this inhibition was then reversed by the addition of 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeable DG, to the assay mixture. The cell proliferation inhibited by forskolin was also restored by the addition of OAG. These data suggest that cAMP inhibits both the activity of protein kinase C (PKC) and consequently cell proliferation through suppression of intracellular DG level, an activator of PKC. Since the inositol 1,4,5-triphosphate level and the hydrolysis of phosphatidylcholine to DG and phosphorylcholine were not affected, forskolin therefore appears to suppress the de novo synthesis of DG.

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Authors and Affiliations

  1. Department of Neurology, Neurological Institute, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812, Fukuoka, Japan

    Takeo Yoshimura, Takuro Kobayashi & Ikuo Goto

  2. Department of Neurology, Kyushu-Kosei-Nenkin Hospital, Kitakyushu, Japan

    Shuichiro Goda

Authors
  1. Takeo Yoshimura
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  2. Takuro Kobayashi
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  3. Shuichiro Goda
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  4. Ikuo Goto
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Yoshimura, T., Kobayashi, T., Goda, S. et al. Inhibition of the proliferation of cultured immortalized schwann cells by forskolin with a decreased basal level of diacylglycerol. Neurochem Res 19, 735–741 (1994). https://doi.org/10.1007/BF00967714

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