Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response
Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response
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DOI：
10.1194/jlr.m200432-jlr200
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发表时间：
2003-04-01
影响因子：
6.5
通讯作者：
Getz, GS
中科院分区：
文献类型：
--
作者：
Cabana, VG;Reardon, CA;Getz, GS
对氧磷酶（PON）的遗传变异与HDL胆固醇和载脂蛋白A-I（apoA-I）相关，提示其具有抗动脉粥样硬化的特性。动脉粥样硬化在人类和兔子中自然发生，但在小鼠中不会发生。我们比较了PON芳基酯酶活性（PON AE酶，苯乙酸底物）在人类，兔子和小鼠的变化。在人类和兔子中，>95%的PON AEase与HDL相关。在小鼠中，约30%的PON AEase是脂质贫乏的。在小鼠中不存在apoA-I的情况下，总PON AEase减少，并且>60%是脂质贫乏的。在注射编码人apoA-I的腺病毒的apoA-I-/-小鼠和以稳态水平表达人apoA-I的转基因小鼠中，PON A-Ease水平和分布恢复。因此，虽然apoA-I不是PON AEase的HDL相关所必需的，但apoA-I的诱导变化与HDL相关的PON AEase的变化相关，但与脂质缺乏的PON AEase无关。PON AEase仅与含apoA-I或apoE的HDL相关，而不与VLDL相关。在缺乏apoA-I和apoE的情况下，PON AEase是全脂质贫乏的。PON AEase是取代HDL的超浓缩和孵育后与血清淀粉样蛋白A。jlr之间的PON分布的变化HDL和脂质贫馏分可能有重要的后果，在其抗氧化活性和动脉粥样硬化。
Genetic variations of paraoxonase (PON) correlate with HDL cholesterol and apolipoprotein A-I (apoA-I), suggesting antiatherogenic properties. Atherosclerosis occurs naturally in humans and rabbits but not in mice. We compared variations of PON arylesterase activity (PON AE-ase, phenylacetate substrate) in humans, rabbits, and mice. In humans and rabbits, >95% of PON AEase is HDL associated. In mice, about 30% of PON AEase is lipid poor. In the absence of apoA-I in mice, total PON AEase is reduced and >60% is lipid poor. PON A-Ease level and distribution is restored in apoA-I-/- mice injected with adenoviruses encoding human apoA-I and in transgenic mice expressing human apoA-I at a steady-state level. Thus, while apoA-I is not required for the HDL association of PON AEase, induced variations in apoA-I correlate with changes in HDL-associated, but not lipid-poor, PON AEase. PON AEase associates only with apoA-I- or apoE-containing HDL but not VLDL. In the absence of both apoA-I and apoE, PON AEase is all-lipid-poor. PON AEase is displaced from HDL by ultracentrifugation and following incubation with serum amyloid A.jlr Variations in the PON distribution between HDL and lipid-poor fractions may have important consequences in its antioxidant activity and in atherogenesis.