Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

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概要

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• ABCA1, a member of the ATP-binding cassette transporter family, regulates high-density lipoprotein (HDL) metabolism and reverses cholesterol transport. Its expression is upregulated mainly by the activation of the liver X receptor (LXR), retinoid X receptor (RXR), and peroxisome proliferator-activated receptors (PPARs). To identify natural compounds that can upregulate ABCA1 expression, we developed a reporter assay using U251-MG (human glioma cell line) cells that stably express a human ABCA1 promoter-luciferase and performed a cell-based high-throughput screening of 118 natural compounds. Using this system, we identified honokiol, a compound extracted from Magnolia officinalis, as an activator of the ABCA1 promoter. We found that honokiol also increased ABCA1 mRNA and protein expression levels in a dose-dependent manner in U251-MG cells without significant cell death and also increased ABCA1, ABCG1 and apolipoprotein E (apoE) expression levels in THP-1 macrophages. PPAR antagonists did not diminish the induction of ABCA1 expression by honokiol in U251-MG cells. Cotreatment of the cells with honokiol and T0901317 (synthetic LXR ligand) further increased the ABCA1 expression level, whereas cotreatment with 9-cis retinoic acid had no additive effect compared with treatment with honokiol alone. We also found that honokiol has binding affinity to RXRβ. In this study, we identified for the first time honokiol as an upregulator of ABCA1 expression, which is mediated by the binding of honokiol to RXRβ as a ligand.

著者

• Woo Je-Tae

  Research Institute for Biological Functions, Chubu University

• CHA Byung-Yoon

  Research Institute for Biological Functions, Chubu University

• Hosono Takashi

  Department Of Chemistry And Life Science Nihon University College Of Bioresouce Sciences

• Yamaguchi Takamasa

  Department Of Biochemistry Faculty Of Pharmaceutical Sciences Science University Of Tokyo

• Michikawa Makoto

  Department Of Dementia Research National Institute For Longevity Sciences

• Jung Cha-gyun

  Department Of Neuro-physiology And Brain Science Nagoya City University Graduate School Of Medical S

• Horike Hirofumi

  Department of Alzheimers Disease Research, Research Institute, National Center for Geriatrics and Ge

• Uhm Kyung-Ok

  Department of Alzheimers Disease Research, Research Institute, National Center for Geriatrics and Ge

• Yamauchi Rena

  Department of Alzheimers Disease Research, Research Institute, National Center for Geriatrics and Ge

• Iida Kagami

  Research Institute for Biological Functions, Chubu University

• Cha Byung-yoon

  Research Institute For Biological Functions Chubu University

• Iida Kagami

  Research Institute For Biological Functions Chubu University

• Yamaguchi Takamasa

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

• Uhm Kyung-Ok

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

• Yamauchi Rena

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

• Jung Cha-Gyun

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

• Michikawa Makoto

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

• Hosono Takashi

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

• Horike Hirofumi

  Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG)

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