Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells
Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells
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DOI：
10.1096/fj.11-182725
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发表时间：
2011-10-01
期刊：
影响因子：
4.8
通讯作者：
Fisher, Edward A.
中科院分区：
文献类型：
--
作者：
Andreo, Ursula;Elkind, Josh;Fisher, Edward A.
VLDL由肝脏产生。其主要蛋白质是apoB 100。二十二碳六烯酸（DHA）是一种膳食多不饱和脂肪酸（PUFA），可降低VLDL水平，用于治疗高脂血症。在模型系统中，DHA通过诱导分泌前apoB 100降解降低VLDL分泌，这一过程依赖于PUFA衍生的脂质过氧化物。我们假设，超氧化物（SO）是一个主要的参与者在DHA诱导的apoB 100降解，鉴于其促进脂质过氧化。SO水平的极低密度脂蛋白代谢模型，大鼠肝癌McArdle细胞，无论是减少模拟超氧化物歧化酶1（SOD 1）或过表达SOD 1或增加SOD 1 siRNA。ApoB 100回收率通过免疫沉淀法评估，SO通过2-羟基乙啶评估，脂质过氧化物通过硫代巴比妥酸反应物质评估。SOD 1模拟物或SOD 1过表达减少SO，并抑制DHA处理的细胞中apoB 100降解高达100%。令人惊讶的是，沉默SOD 1并没有增加DHA诱导的降解，尽管SO的水平更高（+44%）;脂质过氧化物的水平相似，α-生育酚减少了50%的降解。在DHA诱导的apoB 100降解中，脂质过氧化需要SO，但过氧化物水平与降解水平和VLDL产生的调节关系更密切。安德烈，U.，Elkind，J.，Blachford，C. Cederbaum，A.一、Fisher，E. A.超氧阴离子自由基在DHA诱导肝细胞apoB 100降解机制中的作用FASEB J.25，3554-3560（2011）。www.fasebj.org
VLDL is produced by the liver. Its major protein is apoB100. Docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid (PUFA), reduces VLDL levels and is used therapeutically for hypertriglyceridemia. In model systems, DHA lowers VLDL secretion by inducing presecretory apoB100 degradation, a process dependent on PUFA-derived lipid peroxides. We hypothesized that superoxide (SO) was a major participant in DHA-induced apoB100 degradation, given its promotion of lipid peroxidation. SO levels in a model of VLDL metabolism, rat hepatoma McArdle cells, were either decreased by a mimetic of superoxide dismutase 1 (SOD1) or by overexpressing SOD1 or increased by SOD1 siRNA. ApoB100 recovery was assessed by immunoprecipitation, SO by 2-hydroxyethidine, and lipid peroxides by thiobarbituric acid reactive substances. The SOD1 mimetic or SOD1 overexpression reduced SO and inhibited apoB100 degradation in DHA-treated cells by up to 100%. Surprisingly, silencing SOD1 did not increase DHA-induced degradation, although levels of SO were higher (+44%); those of lipid peroxides were similar, and their reduction by alpha-tocopherol decreased degradation by 50%. SO is required for lipid peroxidation in DHA-induced apoB100 degradation, but it is the peroxide level that has a tighter relationship to the level of degradation and the regulation of VLDL production.-Andreo, U., Elkind, J., Blachford, C., Cederbaum, A. I., Fisher, E. A. Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells. FASEB J. 25, 3554-3560 (2011). www.fasebj.org