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

Kazuhiro Omori, Koji Naruishi, Tomoko Yamaguchi, Shun Ai Li, Mayumi Yamaguchi-Morimoto, Kaori Matsuura, Hideo Arai, Kohji Takei, Shogo Takashiba

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalCell and Tissue Research
Volume330
Issue number1
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Cathepsin L
Cyclic AMP Response Element-Binding Protein
Cathepsin B
Cyclosporine
Down-Regulation
Fibroblasts
Cell Survival
Gingival Overgrowth
Cells
DNA
Immunosuppressive Agents
Protein Binding
Human Activities
Plasmids
Enzymes

Keywords

  • Cathepsin
  • CREB
  • Cyclosporin A
  • Gingival fibroblasts
  • Gingival overgrowth
  • Human

ASJC Scopus subject areas

  • Anatomy
  • Clinical Biochemistry
  • Cell Biology

Cite this

cAMP-response element binding protein (CREB) regulates cyclosporine-A- mediated down-regulation of cathepsin B and L synthesis. / Omori, Kazuhiro; Naruishi, Koji; Yamaguchi, Tomoko; Li, Shun Ai; Yamaguchi-Morimoto, Mayumi; Matsuura, Kaori; Arai, Hideo; Takei, Kohji; Takashiba, Shogo.

In: Cell and Tissue Research, Vol. 330, No. 1, 10.2007, p. 75-82.

Research output: Contribution to journalArticle

Omori, Kazuhiro ; Naruishi, Koji ; Yamaguchi, Tomoko ; Li, Shun Ai ; Yamaguchi-Morimoto, Mayumi ; Matsuura, Kaori ; Arai, Hideo ; Takei, Kohji ; Takashiba, Shogo. / cAMP-response element binding protein (CREB) regulates cyclosporine-A- mediated down-regulation of cathepsin B and L synthesis. In: Cell and Tissue Research. 2007 ; Vol. 330, No. 1. pp. 75-82.
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AB - 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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