Astaxanthin Enhances ATP-Binding Cassette Transporter A1/G1 Expressions and Cholesterol Efflux from Macrophages

• Published in: Journal of Nutritional Science and Vitaminology Vol. 58; no. 2; pp. 96 - 104
• Main Authors: IIZUKA, Maki, AYAORI, Makoto, UTO-KONDO, Harumi, YAKUSHIJI, Emi, TAKIGUCHI, Shunichi, NAKAYA, Kazuhiro, HISADA, Tetsuya, SASAKI, Makoto, KOMATSU, Tomohiro, YOGO, Makiko, KISHIMOTO, Yoshimi, KONDO, Kazuo, IKEWAKI, Katsunori
• Format: Journal Article
• Language: English
• Published: Tokyo Center for Academic Publications Japan 2012
• Subjects: ABCA1; ABCG1; Animals; Antioxidants; Apolipoprotein A-I - drug effects; Apolipoprotein A-I - physiology; astaxanthin; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - physiology; Biological and medical sciences; Cardiotonic Agents; Cell Line; Cholesterol - metabolism; cholesterol efflux; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; HDL; Lipoproteins - genetics; Lipoproteins - physiology; Lipoproteins, HDL - drug effects; Lipoproteins, HDL - physiology; Liver X Receptors; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Orphan Nuclear Receptors - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Xanthophylls - pharmacology; ABCA1; HDL; Vertebrata; Mammalia; Astaxanthin; Lipids; Gene expression; cholesterol efflux; ABC transporter; Cholesterol; ABCG1; Macrophage
• ISSN: 0301-4800; 1881-7742
• DOI: 10.3177/jnsv.58.96

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.