A Naturally Occurring Rexinoid, Honokiol, Can Serve as a Regulator of Various Retinoid X Receptor Heterodimers
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概要
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We investigated the properties of honokiol, a natural rexinoid, as a regulator of retinoid X receptor (RXR) heterodimers with various partner nuclear receptors (NRs), in comparison with those of the synthetic rexinoid bexarotene. Honokiol alone was hardly capable of activating peroxisome proliferator-activated receptor (PPAR) γ/RXR, RXR/liver X receptor (LXR), and RXR/vitamin D receptor (VDR) heterodimers, whereas it effectively potentiated their activation by agonists for the partner NRs of the RXR heterodimers. These findings were further supported by increased mRNA and protein levels for the respective NR target genes. Bexarotene alone activated PPARγ/RXR and RXR/LXR heterodimers, but not RXR/VDR heterodimers, and facilitated the activation of all three RXR heterodimers by the respective PPARγ, LXR, and VDR agonists. When the potencies of honokiol and bexarotene were compared, honokiol was able to serve as a subsidiary agonist in the activation of RXR heterodimers in a similar manner to bexarotene. However, it seemed to potentiate the activation of PPARγ/RXR heterodimers by the PPARγ agonist rosiglitazone more efficiently than bexarotene, and was a less potent RXR agonist than bexarotene. In conclusion, we have demonstrated that honokiol is a rexinoid that possesses distinct properties from bexarotene, and mainly has subsidiary roles in the activation of RXR heterodimers by potentiating the activation of RXR heterodimers by agonists for the partner NRs.
著者
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TANABE Hiroki
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University
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Mizukami Hajime
Laboratory Of Pharmacognosy Graduate School Of Pharmaceutical Sciences Nagoya City University
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Inoue Makoto
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University
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Amagaya Sakae
Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University
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Kotani Hitoshi
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University
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