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首页> 外文期刊>Cellular Physiology and Biochemistry >Cell culture conditions determine apolipoprotein CIII secretion and regulation by fibrates in human hepatoma HepG2 cells.
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Cell culture conditions determine apolipoprotein CIII secretion and regulation by fibrates in human hepatoma HepG2 cells.

机译：细胞培养条件决定了人肝癌HepG2细胞中纤维状蛋白的载脂蛋白CIII分泌和调控。

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摘要

Fibrates are widely used drugs which lower triglycerides and increase HDL concentrations in serum. Recent findings from our laboratory have shown that fibrates repress apolipoprotein (apo) CIII gene expression, an effect that explains partially the triglyceride-lowering activity of these drugs. The goal of the present study was to compare the effect of various fibrates on apo CIII gene expression in the human hepatoblastoma cell line HepG2. First, we demonstrate that the level of apo CIII secretion by HepG2 cells is controlled by serum factors whereas apo CIII mRNA levels are not and even increase under conditions when apo CIII secretion dramatically decreases. Twelve different fetal calf serum batches were tested during this study and apo CIII secretion in cell medium could only be detected with three of them. The effect of serum on apolipoprotein secretion was more pronounced for apo CIII whereas other apolipoproteins (apo E, apo B, apo AII and apo AI) were affected to a lesser extent. Under serum conditions allowing apo CIII secretion, treatment with the peroxisome-proliferator activated receptor (PPAR)alpha activators fenofibrate, gemfibrozil and Wy-14643 result in a marked lowering of apo CIII secretion and gene expression, this effect being most pronounced with Wy-14643. Comparison of the activity of a PPARgamma-specific ligand, the antidiabetic thiazolidinedione, BRL-49653 and a PPARalpha ligand Wy-14643 showed a marked decrease of apo CIII secretion and gene expression after activation of PPARalpha but not PPARgamma. In conclusion, fibrates down-regulate apo CIII gene expression in human HepG2 cells, most likely via PPARalpha but not via PPARgamma. However, these effects are only observed in HepG2 cells cultured under appropriate conditions.
机译：贝特类药物是广泛使用的药物，可降低甘油三酸酯并增加血清中的HDL浓度。我们实验室的最新发现表明，贝特类药物抑制载脂蛋白（apo）CIII基因表达，这种作用部分解释了这些药物降低甘油三酸酯的活性。本研究的目的是比较各种贝特类药物对人肝母细胞瘤细胞HepG2中载脂蛋白CIII基因表达的影响。首先，我们证明了HepG2细胞分泌载脂蛋白CIII的水平受血清因素控制，而载脂蛋白CIII分泌显着降低的条件下载脂蛋白CIII mRNA水平却没有甚至增加。在这项研究中测试了十二个不同的胎牛血清批次，只有其中三个可以检测到细胞培养基中的载脂蛋白CIII分泌。血清对载脂蛋白CIII的载脂蛋白分泌的影响更为明显，而其他载脂蛋白（载脂蛋白E，载脂蛋白B，载脂蛋白AII和载脂蛋白AI）受到的影响较小。在允许apo CIII分泌的血清条件下，用过氧化物酶体增殖物激活受体（PPAR）α激活剂非诺贝特，吉非贝齐和Wy-14643进行治疗可导致apo CIII分泌和基因表达显着降低，其中Wy-14643最为明显。比较PPARgamma特异性配体，抗糖尿病药物噻唑烷二酮，BRL-49653和PPARalpha配体Wy-14643的活性，发现在激活PPARalpha而不是PPARgamma后，载脂蛋白CIII分泌和基因表达显着降低。总之，纤维状蛋白下调人类HepG2细胞中载脂蛋白CIII基因的表达，很可能是通过PPARalpha，而不是通过PPARgamma。但是，仅在适当条件下培养的HepG2细胞中观察到了这些作用。

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