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Research ArticleArticle

Scabronine G-Methylester Enhances Secretion of Neurotrophic Factors Mediated by an Activation of Protein Kinase C-ζ

Yutaro Obara, Hironori Kobayashi, Tomihisa Ohta, Yasushi Ohizumi and Norimichi Nakahata
Molecular Pharmacology May 2001, 59 (5) 1287-1297; DOI: https://doi.org/10.1124/mol.59.5.1287
Yutaro Obara
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Hironori Kobayashi
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Tomihisa Ohta
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Yasushi Ohizumi
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Norimichi Nakahata
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Abstract

Glial cells release neurotrophic factors that maintain neurons functionally. Previously, we have shown that the scabronines isolated from Sarcodon scabrosus enhanced the secretion of neurotrophic factors from 1321N1 human astrocytoma cells. In the present study, we examined the mechanism of newly synthesized scabronine G-methylester (ME)-induced secretion of neurotrophic factors from 1321N1 cells. The dramatic neuronal differentiation of rat pheochromocytoma cells (PC-12) was observed by scabronine G-ME-conditioned medium of 1321N1 cells. Scabronine G-ME increased the secretion of nerve growth factor (NGF) and interleukin-6 (IL-6) from 1321N1 cells with the enhancement of their mRNA expressions. Scabronine G-ME concentration-dependently inhibited the carbachol-induced inositol phosphate accumulation in 1321N1 cells, which was reversed by GF109203X, an inhibitor of protein kinase C (PKC) isoforms. Furthermore, GF109203X inhibited the scabronine G-ME-induced mRNA expressions of both NGF and IL-6 and the differentiation of PC-12 cells, showing that scabronine G-ME activated PKC. Although scabronine G-ME enhanced activities of neither conventional nor novel types of PKCs, it translocated PKC-ζ to membranes in intact cells and cell-free condition. Furthermore, recombinant PKC-ζ activity was also increased by scabronine G-ME, suggesting the involvement of PKC-ζ in the effect of scabronine G-ME. Concerning the downstream effectors of the PKC-ζ, scabronine G-ME translocated nuclear factor-κB to nucleus, and enhanced its transcriptional activity. In addition, scabronine G-ME caused the degradation of inhibitor of nuclear factor-κB concentration-dependently, which was inhibited by GF109203X. These results suggest that scabronine G-ME potentially enhances the secretion of neurotrophic factors from 1321N1 cells mediated via the activation of PKC-ζ.

Footnotes

    • Received May 23, 2000.
    • Accepted January 23, 2001.
  • Send reprint requests to: Norimichi Nakahata, Ph.D, Professor, Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. E-mail: nakahata{at}mail.pharm.tohoku.ac.jp

  • This work was partly supported by Grants-in-Aid 08672496 and 09470497 (N.N.) from Scientific Research from the Ministry of Education, Science, Sport and Culture of Japan, and from Japan Society for the Promotion of Science Grant 01532 (Yu.O.).

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Molecular Pharmacology: 59 (5)
Molecular Pharmacology
Vol. 59, Issue 5
1 May 2001
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Research ArticleArticle

Scabronine G-Methylester Enhances Secretion of Neurotrophic Factors Mediated by an Activation of Protein Kinase C-ζ

Yutaro Obara, Hironori Kobayashi, Tomihisa Ohta, Yasushi Ohizumi and Norimichi Nakahata
Molecular Pharmacology May 1, 2001, 59 (5) 1287-1297; DOI: https://doi.org/10.1124/mol.59.5.1287

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Research ArticleArticle

Scabronine G-Methylester Enhances Secretion of Neurotrophic Factors Mediated by an Activation of Protein Kinase C-ζ

Yutaro Obara, Hironori Kobayashi, Tomihisa Ohta, Yasushi Ohizumi and Norimichi Nakahata
Molecular Pharmacology May 1, 2001, 59 (5) 1287-1297; DOI: https://doi.org/10.1124/mol.59.5.1287
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