2007年10月
cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis
CELL AND TISSUE RESEARCH
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- 巻
- 330
- 号
- 1
- 開始ページ
- 75
- 終了ページ
- 82
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1007/s00441-007-0457-8
- 出版者・発行元
- SPRINGER
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.
- リンク情報
- ID情報
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- DOI : 10.1007/s00441-007-0457-8
- ISSN : 0302-766X
- Web of Science ID : WOS:000249618700008