Riccardin C: a natural product that functions as a liver X receptor (LXR)alpha agonist and an LXRbeta antagonist.
Liver X receptors (LXRs) alpha and beta share considerable sequence homology and several functions, respond to the same endogenous and synthetic ligands, and play critical roles in maintaining lipid homeostasis. In this study, liverwort-derived riccardin C (RC) and F (RF) were identified as an LXRalpha agonist/LXRbeta antagonist and an LXRalpha antagonist, respectively. RC and RF bound to LXRs, but had different abilities to recruit a coactivator and thereby induce transactivation. Despite its unique subtype-selective activity, RC enhanced ABCA1 and ABCG1 expression and cellular cholesterol efflux in THP-1 cells. RC may provide a novel tool for identifying subtype-function and drug development.
Tamehiro
Norimasa
N
National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Sato
Yoji
Y
Suzuki
Takuo
T
Hashimoto
Toshihiro
T
Asakawa
Yoshinori
Y
Yokoyama
Shinji
S
Kawanishi
Tohru
T
Ohno
Yasuo
Y
Inoue
Kazuhide
K
Nagao
Taku
T
Nishimaki-Mogami
Tomoko
T
D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001688:Biological Products; D004268:DNA-Binding Proteins; D004988:Ethers, Cyclic; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C505660:riccardin C