cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis
cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis
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DOI：
10.1007/s00441-007-0457-8
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发表时间：
2007-10-01
影响因子：
3.6
通讯作者：
Takashiba, Shogo
中科院分区：
文献类型：
--
作者：
Omori, Kazuhiro;Naruishi, Koji;Takashiba, Shogo
环孢菌素A（CsA）是一种免疫抑制剂，具有严重的副作用，包括牙龈增生。我们以前曾报道，CsA损害的活性溶酶体酶组织蛋白酶B和L在人牙龈成纤维细胞（HGF）。在这里，我们已经检查了环腺苷酸反应元件结合蛋白（CREB）和细胞活力的DNA结合活性的影响，和CREB对组织蛋白酶B和L的合成和活性在HGF的影响。我们已经证实，CsA下调组织蛋白酶B和L的合成。此外，CsA对细胞活力没有影响，并显著损害CREB-DNA结合活性。重要的是，在用表达显性阴性CREB的质粒转染的HGF中，组织蛋白酶B和L的合成下调，并且它们的活性也显著受损。这些结果表明，CREB是必不可少的CsA介导的下调组织蛋白酶B和L的合成在HGF。
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.