期刊
ATHEROSCLEROSIS
卷 192, 期 2, 页码 266-274出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2006.07.017
关键词
atherosclerosis; apoA-IV; conjugated dienes; copper; lipid hydroperoxides; oxidised low density lipoprotein
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R23HL030897, R01HL030897] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL30897, R01 HL030897, R01 HL030897-23] Funding Source: Medline
Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating potential anti-atherogenic properties. The aim of this study was to investigate how the inhibition of low density lipoprotein (LDL) oxidation was influenced by common apoA-IV isoforms. Recombinant wild type apoA-IV (100 mu g/ml) significantly inhibited the oxidation of LDL (50 mu g protein/ml) by 5 mu M CuSO(4) (P < 0.005), but not by 100 mu M CuSO(4), suggesting that it may act by binding copper ions. ApoA-IV also inhibited the oxidation of LDL by the water-soluble free-radical generator 2,2'-azobis(amidinopropane) dihydrochloride (AAPH; I mM), as shown by the two-fold increase in the time for half maximal conjugated diene formation (T(1/2); P < 0.05) suggesting it can also scavenge free radicals in the aqueous phase. Compared to wild type apoA-IV, apoA-IV-S347 decreased T(1/2) by 15% (P = 0.036) and apoA-IV-H360 increased T(1/2) by 18% (P = 0.046). All apoA-IV isoforms increased the relative electrophoretic mobility of native LDL, suggesting apoA-IV can bind to LDL and acts as a site-specific antioxidant. The reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV may account for the previous association of the APOA4 S347 variant with increased CHD risk and oxidative stress. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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