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cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis

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Abstract

Cyclosporin A (CsA) is an immunosuppressant with severe side effects including gingival overgrowth. We have previously reported that CsA impairs the activity of the lysosomal enzymes cathepsin B and L in human gingival fibroblasts (HGFs). Here, we have examined the effects of CsA on the DNA-binding activity of the cyclic AMP response element-binding protein (CREB) and cell viability, and the effects of CREB on cathepsin B and L synthesis and activity in HGFs. We have confirmed that CsA down-regulates cathepsin B and L synthesis. Further, CsA has no effect on cell viability and dramatically impairs CREB-DNA binding activity. Importantly, the synthesis of cathepsin B and L is down-regulated, and their activity is also significantly impaired in HGFs transfected with plasmid expressing dominant-negative CREB. These results suggest that CREB is essential for the CsA-mediated down-regulation of cathepsin B and L synthesis in HGFs.

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Acknowledgement

We greatly thank Scott Messenger at NASA Johnson Space Center for the revision of the manuscript and for encouragement in our research.

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Author notes

  1. Mayumi Yamaguchi-Morimoto

    Present address: Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi-ku, Hiroshima, 734-8553, Japan

Authors and Affiliations

  1. Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8525, Japan

    Kazuhiro Omori, Koji Naruishi, Tomoko Yamaguchi, Mayumi Yamaguchi-Morimoto, Kaori Matsuura, Hideo Arai & Shogo Takashiba

  2. Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Shun-Ai Li & Kohji Takei

Authors
  1. Kazuhiro Omori
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  2. Koji Naruishi
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  3. Tomoko Yamaguchi
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  4. Shun-Ai Li
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  5. Mayumi Yamaguchi-Morimoto
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  7. Hideo Arai
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  9. Shogo Takashiba
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Corresponding author

Correspondence to Shogo Takashiba.

Additional information

This work was supported by a Grant-in-Aid for Young Scientists (B 18791592 to K.N.) from the Japan Society for the Promotion of Science.

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Omori, K., Naruishi, K., Yamaguchi, T. et al. cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis. Cell Tissue Res 330, 75–82 (2007). https://doi.org/10.1007/s00441-007-0457-8

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  • DOI: https://doi.org/10.1007/s00441-007-0457-8

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