RRC ID 44471
著者 Nakaya K, Ayaori M, Uto-Kondo H, Sotherden GM, Nishida T, Katamoto H, Miura Y, Takiguchi S, Yakushiji E, Iizuka M, Ogura M, Sasaki M, Yogo M, Komatsu T, Adachi T, Maruyama C, Ikewaki K.
タイトル Overexpression of stearoyl-coenzyme A desaturase 1 in macrophages promotes reverse cholesterol transport.
ジャーナル Biochim Biophys Acta
Abstract Stearoyl-coenzyme A desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. However, the impact of SCD1 on atherosclerosis remains unclear. The aim of this study was to determine whether SCD1 affects macrophage reverse cholesterol transport (RCT) in mice. Compared to the control, adenoviral-mediated SCD1 overexpression in RAW264.7 macrophages increased cholesterol efflux to HDL, but not to apoA-I, without clear changes in ABCA1, ABCG1 and SR-BI expressions. While knockdown of ABCG1 and SR-BI did not affect the SCD1-induced cholesterol efflux to HDL, SCD1-overexpressing macrophages promoted the formation of both normal- and large-sized HDL in media, accompanying increased apolipoprotein A-I levels in HDL fractions. Transformation to larger particles of HDL was independently confirmed by nuclear magnetic resonance-based lipoprotein analysis. Interestingly, media transfer assays revealed that HDL generated by SCD1 had enhanced cholesterol efflux potential, indicating that SCD1 transformed HDL to a more anti-atherogenic phenotype. To study macrophage RCT in vivo, (3)H-cholesterol-labeled RAW264.7 cells overexpressing SCD1 or the control were intraperitoneally injected into mice. Supporting the in vitro data, injection of SCD1-macrophages resulted in significant increases in (3)H-tracer in plasma, liver, and feces compared to the control. Moreover, there was a shift towards larger particles in the (3)H-tracer distribution of HDL fractions obtained from the mice. In conclusion, macrophage-specific SCD1 overexpression promotes overall RCT through increased cholesterol efflux to HDL, suggesting that macrophage SCD1 achieves an anti-atherogenic effect by enhancing RCT.
巻・号 1831(8)
ページ 1402-11
公開日 2013-8-1
DOI 10.1016/j.bbalip.2013.05.009
PII S1388-1981(13)00123-6
PMID 23747827
MeSH ATP Binding Cassette Transporter 1 ATP Binding Cassette Transporter, Subfamily G, Member 1 ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism Animals Atherosclerosis / enzymology Atherosclerosis / genetics Atherosclerosis / pathology Atherosclerosis / therapy Biological Transport, Active / genetics Cell Line Cholesterol / genetics Cholesterol / metabolism* Gene Expression Regulation, Enzymologic* Humans Lipoproteins / genetics Lipoproteins / metabolism Lipoproteins, HDL / genetics Lipoproteins, HDL / metabolism* Macrophages / enzymology* Macrophages / pathology Mice Stearoyl-CoA Desaturase / biosynthesis* Stearoyl-CoA Desaturase / genetics
IF 3.411
引用数 10
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)