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
N1 - Funding 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.
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 - CREB
KW - Cathepsin
KW - Cyclosporin A
KW - Gingival fibroblasts
KW - Gingival overgrowth
KW - Human
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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 - Zeitschrift für Zellforschung und mikroskopische Anatomie (Vienna, Austria : 1948)
JF - Zeitschrift für Zellforschung und mikroskopische Anatomie (Vienna, Austria : 1948)
SN - 0302-766X
IS - 1
ER -
