| RRC ID |
43951
|
| 著者 |
Iizuka M, Ayaori M, Uto-Kondo H, Yakushiji E, Takiguchi S, Nakaya K, Hisada T, Sasaki M, Komatsu T, Yogo M, Kishimoto Y, Kondo K, Ikewaki K.
|
| タイトル |
Astaxanthin enhances ATP-binding cassette transporter A1/G1 expressions and cholesterol efflux from macrophages.
|
| ジャーナル |
J Nutr Sci Vitaminol (Tokyo)
|
| Abstract |
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.
|
| 巻・号 |
58(2)
|
| ページ |
96-104
|
| 公開日 |
2012-1-1
|
| DOI |
10.3177/jnsv.58.96
|
| PII |
DN/JST.JSTAGE/jnsv/58.96
|
| PMID |
22790567
|
| MeSH |
ATP Binding Cassette Transporter 1
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters / genetics*
ATP-Binding Cassette Transporters / physiology
Animals
Antioxidants
Apolipoprotein A-I / drug effects
Apolipoprotein A-I / physiology
Cardiotonic Agents
Cell Line
Cholesterol / metabolism*
Gene Expression / drug effects*
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
Xanthophylls / pharmacology
|
| IF |
1.424
|
| 引用数 |
22
|
|
WOS 分野
|
NUTRITION & DIETETICS
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535)
THP-1(RCB1189) |
