A high-throughput screen for inhibitors of the prolyl isomerase,Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation |
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| Authors: | Tadashi Mori Masafumi Hidaka Hiroko Ikuji Ibuki Yoshizawa Haruhiko Toyohara Toru Okuda |
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| Affiliation: | 1. Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;2. Graduate School of Agriculture, Kyoto University, Kyoto, Japan;3. Tamagawa University, Research Center, Tokyo, Japan |
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| Abstract: | The peptidyl prolyl cis/trans isomerase Pin1 enhances the uptake of triglycerides and the differentiation of fibroblasts into adipose cells in response to insulin stimulation. Pin1 downregulation could be a potential approach to prevent and treat obesity-related disorders. In order to identify an inhibitor of Pin1 that exhibited minimal cytotoxicity, we established a high-throughput screen for Pin1 inhibitors and used this method to identify an inhibitor from 1,056 crude fractions of two natural product libraries. The candidate, a phlorotannin called 974-B, was isolated from the seaweed, Ecklonia kurome. 974-B inhibited the differentiation of mouse embryonic fibroblasts and 3T3-L1 cells into adipose cells without inducing cytotoxicity. We discovered the Pin1 inhibitor, 974-B, from the seaweed, E. kurome, and showed that it blocks the differentiation of fibroblasts into adipose cells, suggesting that 974-B could be a lead drug candidate for obesity-related disorders. |
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| Keywords: | seaweed polyphenol adipose cell obesity high-throughput screen prolyl isomerase |
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