TY - JOUR
T1 - Screening of novel nuclear receptor agonists by a convenient reporter gene assay system using green fluorescent protein derivatives
AU - Suzuki, T.
AU - Nishimaki-Mogami, T.
AU - Kawai, H.
AU - Kobayashi, T.
AU - Shinozaki, Y.
AU - Sato, Y.
AU - Hashimoto, T.
AU - Asakawa, Y.
AU - Inoue, K.
AU - Ohno, Y.
AU - Hayakawa, T.
AU - Kawanishi, T.
N1 - Funding Information:
This work was supported by a grant-in-aid (MF-16) from the Pharmaceuticals and Medical Device Agency, a grant-in-aid for Research on Health Sciences Focusing on Drug Innovation from the Japan Health Science Foundation, and a grant-in-aid for Research on Advanced Medical Technology from the Ministry of Health, Labour and Welfare of Japan.
PY - 2006/6/12
Y1 - 2006/6/12
N2 - Nuclear receptors represent a very good family of protein targets for the prevention and treatment of diverse diseases. In this study, we screened natural compounds and their derivatives, and discovered ligands for the retinoic acid receptors (RARs) and the farnesoid X receptor (FXR). In the reporter assay systems of nuclear receptors presented here, two fluorescent proteins, enhanced yellow fluorescent protein (EYFP) and enhanced cyan fluorescent protein (ECFP), were used for detection of a ligand-based induction and as an internal control, respectively. By optimizing the conditions (e.g., of hormone response elements and promoter genes for reporter plasmids), we established a battery of assay systems for ligands of RARs, retinoid X receptor (RXR) and FXR. The screening using the reporter assay system can be carried out without the addition of co-factors or substrates. As a result of screening of more than 140 compounds, several compounds were detected which activate RARs and/or FXR. Caffeic acid phenylethyl ester (CAPE), known as a component of propolis from honeybee hives, and other derivatives of caffeic acid up-regulated the expression of reporter gene for RARs. Grifolin and ginkgolic acids, which are non-steroidal skeleton compounds purified from mushroom or ginkgo leaves, up-regulated the expression of the reporter gene for FXR.
AB - Nuclear receptors represent a very good family of protein targets for the prevention and treatment of diverse diseases. In this study, we screened natural compounds and their derivatives, and discovered ligands for the retinoic acid receptors (RARs) and the farnesoid X receptor (FXR). In the reporter assay systems of nuclear receptors presented here, two fluorescent proteins, enhanced yellow fluorescent protein (EYFP) and enhanced cyan fluorescent protein (ECFP), were used for detection of a ligand-based induction and as an internal control, respectively. By optimizing the conditions (e.g., of hormone response elements and promoter genes for reporter plasmids), we established a battery of assay systems for ligands of RARs, retinoid X receptor (RXR) and FXR. The screening using the reporter assay system can be carried out without the addition of co-factors or substrates. As a result of screening of more than 140 compounds, several compounds were detected which activate RARs and/or FXR. Caffeic acid phenylethyl ester (CAPE), known as a component of propolis from honeybee hives, and other derivatives of caffeic acid up-regulated the expression of reporter gene for RARs. Grifolin and ginkgolic acids, which are non-steroidal skeleton compounds purified from mushroom or ginkgo leaves, up-regulated the expression of the reporter gene for FXR.
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U2 - 10.1016/j.phymed.2005.09.003
DO - 10.1016/j.phymed.2005.09.003
M3 - Article
C2 - 16716909
AN - SCOPUS:33646576558
SN - 0944-7113
VL - 13
SP - 401
EP - 411
JO - Phytomedicine
JF - Phytomedicine
IS - 6
ER -