Astaxanthin Enhances ATP-Binding Cassette Transporter A1/G1 Expressions and Cholesterol Efflux from Macrophages
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- IIZUKA Maki
- Institute of Environmental Science for Human Life, Ochanomizu University Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- AYAORI Makoto
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- UTO-KONDO Harumi
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- YAKUSHIJI Emi
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- TAKIGUCHI Shunichi
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- NAKAYA Kazuhiro
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- HISADA Tetsuya
- Department of Public Health and Preventive Medicine, National Defense Medical College
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- SASAKI Makoto
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- KOMATSU Tomohiro
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- YOGO Makiko
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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- KISHIMOTO Yoshimi
- Institute of Environmental Science for Human Life, Ochanomizu University
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- KONDO Kazuo
- Institute of Environmental Science for Human Life, Ochanomizu University
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- IKEWAKI Katsunori
- Division of Anti-aging, Department of Internal Medicine, National Defense Medical College
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ATP-binding cassette transporters (ABC) A1 and G1 are key molecules in cholesterol efflux from macrophages, which is an initial step of reverse cholesterol transport (RCT), a major anti-atherogenic property of high-density lipoprotein (HDL). Astaxanthin is one of the naturally occurring carotenoids responsible for the pink-red pigmentation in a variety of living organisms. Although astaxanthin is known to be a strong antioxidant, it remains unclear through what mechanism of action it affects cholesterol homeostasis in macrophages. We therefore investigated the effects of astaxanthin on cholesterol efflux and ABCA1/G1 expressions in macrophages. Astaxanthin enhanced both apolipoprotein (apo) A-I- and HDL-mediated cholesterol efflux from RAW264.7 cells. In supporting these enhanced cholesterol efflux mechanisms, astaxanthin promoted ABCA1/G1 expression in various macrophages. In contrast, peroxisome proliferator-activated receptor γ, liver X receptor (LXR) α and LXRβ levels remained unchanged by astaxanthin. An experiment using actinomycin D demonstrated that astaxanthin transcriptionally induced ABCA1/G1 expression, and oxysterol depletion caused by overexpression of cholesterol sulfotransferase further revealed that these inductions in ABCA1/G1 were independent of LXR-mediated pathways. Finally, we performed luciferase assays using human ABCA1/G1 promoter-reporter constructs to reveal that astaxanthin activated both promoters irrespective of the presence or absence of LXR-responsive elements, indicating LXR-independence of these activations. In conclusion, astaxanthin increased ABCA1/G1 expression, thereby enhancing apoA-I/HDL-mediated cholesterol efflux from the macrophages in an LXR-independent manner. In addition to the anti-oxidative properties, the potential cardioprotective properties of astaxanthin might therefore be associated with an enhanced anti-atherogenic function of HDL.
収録刊行物
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- Journal of Nutritional Science and Vitaminology
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Journal of Nutritional Science and Vitaminology 58 (2), 96-104, 2012
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詳細情報 詳細情報について
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- CRID
- 1390282681302421504
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- NII論文ID
- 130002103037
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- NII書誌ID
- AA00703822
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- COI
- 1:CAS:528:DC%2BC38XmsFymt70%3D
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- ISSN
- 18817742
- 03014800
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- NDL書誌ID
- 023599539
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- PubMed
- 22790567
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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