RRC ID 67894
著者 Inoue M, Tanabe H, Nakashima K, Ishida Y, Kotani H.
タイトル Rexinoids isolated from Sophora tonkinensis with a gene expression profile distinct from the synthetic rexinoid bexarotene.
ジャーナル J Nat Prod
Abstract The retinoid X receptor (RXR) plays a critical role in transcriptional regulation via formation of an RXR homodimer or heterodimers with partner nuclear receptors. Despite the numerous beneficial effects, only a limited number of naturally occurring RXR agonists are known. In this report, two prenylated flavanones (1 and 2) isolated from Sophora tonkinensis were identified as new rexinoids that preferentially activated RXRs, relative to the retinoic acid receptor. The activities of 1 and 2 were the most potent among naturally occurring rexinoids, yet 2 orders of magnitude lower than the synthetic rexinoid bexarotene. Compounds 1 and 2 activated particular RXR heterodimers in a manner similar to bexarotene. A microarray assay followed by quantitative real-time polymerase chain reaction analyses on RNAs isolated from C2C12 myotubes treated with 1 or 2 demonstrated that they significantly increased mRNA levels of lipoprotein lipase, angiopoietin-like protein 4, and heme oxygenase-1. In contrast, bexarotene preferentially potentiated transcription of genes involved in lipogenesis and lipid metabolism such as sterol regulatory element-binding protein-1, fatty acid synthase, and apolipoprotein D by a liver X receptor agonist. In this study, we have demonstrated that two newly identified naturally occurring rexinoids, 1 and 2, possess properties different from bexarotene.
巻・号 77(7)
ページ 1670-7
公開日 2014-7-25
DOI 10.1021/np5002016
PMID 24959987
MeSH Anticarcinogenic Agents / chemistry Anticarcinogenic Agents / pharmacology Bexarotene Flavanones / chemistry Flavanones / pharmacology* Gene Expression Gene Expression Regulation Heme Oxygenase-1 / metabolism Liver X Receptors Molecular Structure Orphan Nuclear Receptors PPAR gamma / metabolism RNA, Messenger / metabolism Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Retinoid X Receptors / physiology* Signal Transduction Sophora / chemistry* Tetrahydronaphthalenes / chemical synthesis* Tetrahydronaphthalenes / chemistry Tetrahydronaphthalenes / pharmacology Transcriptome*
IF 3.782
リソース情報
ヒト・動物細胞 293(RCB1637) RAW 264(RCB0535) C2C12(RCB0987)