| Selection and optimization of MCF-7 cell line for screening selective inhibitors of 11beta-hydroxysteroid dehydrogenase 2. | |
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MedLine Citation:
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PMID: 20629036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) produces glucocorticoid (GC) from 11-keto metabolite, and its modulation has been suggested as a novel approach to treat metabolic diseases. In contrast, type 2 isozyme 11beta-HSD2 is involved in the inactivation of glucocorticoids (GCs), protecting the non-selective mineralocorticoid receptor (MR) from GCs in kidney. Therefore, when 11beta-HSD1 inhibitors are pursued to treat the metabolic syndrome, preferential selectivity of inhibitors for type 1 over type 2 isozyme is rather important than inhibitory potency. Primarily, to search for cell lines with 11beta-HSD2 activity, we investigated the expression profiles of enzymes or receptors relevant to GC metabolism in breast, colon, and bone-derived cell lines. We demonstrated that MCF-7 cells had high expression for 11beta-HSD2, but not for 11beta-HSD1 with its cognate receptor. Next, for the determination of enzyme activity indirectly, we adopted homogeneous time resolved fluorescence (HTRF) cortisol assay. Obviously, the feasibility of HTRF to cellular 11beta-HSD2 was corroborated by constructing inhibitory response to an 11b-HSD2 inhibitor glycyrrhetinic acid (GA). Taken together, MCF-7 that overexpresses type 2 but not type 1 enzyme is chosen for cellular 11beta-HSD2 assay, and our results show that a nonradioactive HTRF assay is applicable for type 2 as well as type 1 isozyme. |
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Authors:
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Chi Hyun Kim; Young Sik Cho |
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Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell biochemistry and function Volume: 28 ISSN: 1099-0844 ISO Abbreviation: Cell Biochem. Funct. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2010-12-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8305874 Medline TA: Cell Biochem Funct Country: England |
Other Details:
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Languages: eng Pagination: 440-7 Citation Subset: IM |
Affiliation:
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Division of Electron Microscopic Research, Korea Basic Science Institute, 113 Gwahangno, Yuseong-gu, Daejeon, South Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenase Type 2
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analysis,
antagonists & inhibitors*,
metabolism Cell Line, Tumor Drug Screening Assays, Antitumor / methods* Enzyme Assays / methods Enzyme Inhibitors / pharmacology* Humans Hydrocortisone / analysis, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 50-23-7/Hydrocortisone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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