Triglyceride accumulation by peroxisome proliferators in rat hepatocytes.
Triglyceride accumulation by peroxisome proliferators in rat hepatocytes.
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大鼠肝细胞中过氧化物酶体增殖剂积累甘油三酯。
DOI：
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发表时间：
2007
影响因子：
2
通讯作者：
M. Miyake
中科院分区：
文献类型：
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作者：
H. Kawano;Tomomi Nagata;M. Narahara;M. Kanazawa;M. Miyake
过氧化物酶体增殖物（PxPs）在啮齿动物肝脏中诱导过氧化物酶体β氧化（Px-ox）并具有降血脂功能。为了研究PxPs的降血脂作用，我们在原代培养的大鼠肝细胞中研究了TG波动与PxPs功能指标Px-ox活性之间的关系。纳菲诺平（Nafenopin, Nf）处理肝细胞导致Px-ox活性增加，并与细胞TG积累呈时间依赖性，相关系数r=0.918。利用不同结构的PxPs获得了活性与细胞TG之间的关系，相关系数r=0.747。治疗降血脂药物普伐他汀，但非pxp，降低TG在培养基中，但对细胞TG和Px-ox活性没有影响。甘油三酯总量和甘油三酯新合成途径最后一酶二酰基甘油酰基转移酶活性不受Nf处理的影响。Brefeldin A培养肝细胞时，细胞TG积累，与Nf相同，但Px-ox活性未增强。经Western blot分析，Nf处理显著降低了条件培养基制备的极低密度脂蛋白（VLDL）组分的载脂蛋白B （apo B）水平，提高了细胞载脂蛋白B的水平。微粒体甘油三酯转移蛋白活性不受Nf的影响。综上所述，关于PxPs降低TG的作用，提示PxPs引起TG在肝细胞的蓄积，但不影响TG的生物合成和VLDL的构建，可能对VLDL的分泌过程有抑制作用。
Peroxisome proliferators (PxPs) induce peroxisomal beta-oxidation (Px-ox) in the liver of rodents and have a hypolipidemic function. To investigate hypolipidemic effect of PxPs, the relationship between TG fluctuation and Px-ox activity, as an indicator of the function of PxPs, was studied in primary cultured rat hepatocytes. Nafenopin (Nf) treatment of hepatocytes caused an increase in Px-ox activity in association with cellular TG accumulation in a time-dependent manner with a coefficient of r=0.918. This relationship between the activity and cellular TG were obtained using structurally diverse PxPs with a correlation coefficient of r=0.747. Treatment of the hypolipidemic drug, but non-PxP Pravastatin, decreased TG in the medium, but did not have the effects on cellular TG and Px-ox activity. The total amount of TG and diacylglycerol acyltransferase activity, the last enzyme in the TG de novo synthesis pathway, were not affected by Nf treatment. When hepatocytes were cultured with Brefeldin A, cellular TG was accumulated, the same as with Nf, however, Px-ox activity was not enhanced. Nf treatment markedly decreased the level of apolipoprotein B (apo B) in very low density lipoprotein (VLDL) fractions prepared from conditioned media and increased that of cellular apoB by Western blot analysis. Microsomal triglyceride transfer protein activity was not influenced by Nf. Together, with regards to TG lowering effect of PxPs, it is suggested that PxPs cause hepatocellular accumulation of TG without effects on TG biosynthesis and VLDL construction, and they might have inhibitory effect on VLDL secretion process.
影响因子：
56.9
作者：
J. Wetterau;L. Aggerbeck;M. Bouma;C. Eisenberg;A. Munck;M. Hermier;J. Schmitz;G. Gay;D. Rader
通讯作者：
J. Wetterau;L. Aggerbeck;M. Bouma;C. Eisenberg;A. Munck;M. Hermier;J. Schmitz;G. Gay;D. Rader