Cho K H, Park S H, Han J M, Kim H C, Choi Y K, Choi I
School of Biotechnology, Yeungnam University, Gyeongsan, South Korea.
Eur J Clin Invest. 2006 Dec;36(12):875-82. doi: 10.1111/j.1365-2362.2006.01737.x.
Two mutants of apolipoprotein (apo) A-I, V156K and A158E, showed markedly different structural and functional properties in lipid-free and lipid-bound states in the authors' earlier report. The physiological activities of these mutants were compared with the wild-type (WT) and R173C mutant using in vitro and in vivo experiments.
A reconstituted high-density lipoprotein (rHDL) with palmitoyloleoyl phosphatidylcholine (POPC), combined with each of the apoA-I variants, was injected into the tail-veins of hypercholesterolaemic mice (C57BL6/J), which had been fed a high cholesterol and high fat (HCHF; 0.5% cholesterol, 15% lard, 0.1% sodium cholate) diet for 23 weeks, once at 0 h and then every 24 h, at a dosage of 30 mg apoA-I kg(-1) of body-weight.
The V156K-rHDL and R173C-rHDL exhibited significantly stronger anti-oxidant activity against copper-mediated low-density lipoprotein (LDL) oxidation than did A158E in an apolipoprotein state. The mice injected with WT-rHDL or A158E-rHDL showed abrupt increases in total cholesterol concentrations (47% and 38%, respectively) as compared with the levels before injection, whereas the mice injected with V156K-rHDL and R173C-rHDL did not. Injection with V156K-rHDL improved serum lipids and anti-oxidative activities compared with the injection of WT-rHDL. Injection of WT-rHDL or A158E-rHDL increased serum interleukin-6 (IL-6) to 90-110 pg mL(-1), whereas the injection of V156K-rHDL or R173C-rHDL increased serum IL-6 to 17-25 pg mL(-1) only.
The V156K-rHDL and R173C-rHDL displayed potent beneficial effects, including anti-oxidant and anti-inflammatory activity from both in vitro and in vivo evaluations, whereas the WT-rHDL and A158E-rHDL did not.
在作者早期的报告中，载脂蛋白（apo）A-I的两种突变体V156K和A158E在无脂和脂结合状态下表现出明显不同的结构和功能特性。通过体外和体内实验比较了这些突变体与野生型（WT）及R173C突变体的生理活性。
将含有棕榈油酰油酰磷脂酰胆碱（POPC）并结合每种apoA-I变体的重组高密度脂蛋白（rHDL），以30mg apoA-I kg(-1)体重的剂量，于0小时注射一次，然后每24小时注射一次，注入喂食高胆固醇和高脂肪（HCHF；0.5%胆固醇、15%猪油、0.1%胆酸钠）饮食23周的高胆固醇血症小鼠（C57BL6/J）的尾静脉中。
在载脂蛋白状态下，V156K-rHDL和R173C-rHDL对铜介导的低密度脂蛋白（LDL）氧化表现出比A158E更强的抗氧化活性。注射WT-rHDL或A158E-rHDL的小鼠与注射前相比，总胆固醇浓度急剧升高（分别为47%和38%），而注射V156K-rHDL和R173C-rHDL的小鼠则没有。与注射WT-rHDL相比，注射V156K-rHDL改善了血脂和抗氧化活性。注射WT-rHDL或A158E-rHDL使血清白细胞介素-6（IL-6）升高至90 - 110 pg mL(-1)，而注射V156K-rHDL或R173C-rHDL仅使血清IL-6升高至17 - 25 pg mL(-1)。
体外和体内评估均显示，V156K-rHDL和R173C-rHDL具有强大的有益作用，包括抗氧化和抗炎活性，而WT-rHDL和A158E-rHDL则没有。
