Astaxanthin Enhances ATP-Binding Cassette Transporter A1/G1 Expressions and Cholesterol Efflux from Macrophages
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概要
- 論文の詳細を見る
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.
著者
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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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Hisada Tetsuya
Department Of Internal Medicine National Defence Medical College
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Ayaori Makoto
Internal Medicine I Medical Research Center National Defense Medical College
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KISHIMOTO Yoshimi
Institute of Environmental Science for Human Life, Ochanomizu University
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IIZUKA Maki
Institute of Environmental Science for Human Life, Ochanomizu University
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Kishimoto Yoshimi
Institute Of Environmental Science For Human Life Ochanomizu University
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Sasaki Makoto
Division Of Hematology Department Of Internal Medicine Juntendo University School Of Medicine
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Ayaori Makoto
Division Of Anti-aging Department Of Internal Medicine National Defense Medical College
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Iizuka Maki
Institute Of Environmental Science For Human Life Ochanomizu University
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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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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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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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