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 language | English |
|---|---|
| Pages (from-to) | 75-82 |
| Number of pages | 8 |
| Journal | Cell and Tissue Research |
| Volume | 330 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 2007 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - cAMP-response element binding protein (CREB) regulates cyclosporine-A- mediated down-regulation of cathepsin B and L synthesis
AU - Omori, Kazuhiro
AU - Naruishi, Koji
AU - Yamaguchi, Tomoko
AU - Li, Shun Ai
AU - Yamaguchi-Morimoto, Mayumi
AU - Matsuura, Kaori
AU - Arai, Hideo
AU - Takei, Kohji
AU - Takashiba, Shogo
PY - 2007/10
Y1 - 2007/10
N2 - 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.
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.
KW - Cathepsin
KW - CREB
KW - Cyclosporin A
KW - Gingival fibroblasts
KW - Gingival overgrowth
KW - Human
UR - http://www.scopus.com/inward/record.url?scp=34548760230&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548760230&partnerID=8YFLogxK
U2 - 10.1007/s00441-007-0457-8
DO - 10.1007/s00441-007-0457-8
M3 - Article
C2 - 17724614
AN - SCOPUS:34548760230
VL - 330
SP - 75
EP - 82
JO - Cell and Tissue Research
JF - Cell and Tissue Research
SN - 0302-766X
IS - 1
ER -