首页> 外文期刊>Biochimica et Biophysica Acta. Molecular and cell biology of Lipids >Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues
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Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

机译:无法完全抑制胚胎和胚外胎儿组织中外源性固醇的固醇合成速率

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The requirement for cholesterol is greater in developing tissues (fetus, placenta, and yolk sac) as compared to adult tissues. Here, we compared cholesterol-induced suppression of sterol synthesis rates in the adult liver to the fetal liver, fetal body, placenta, and yolk sac of the Golden Syrian hamster. Sterol synthesis rates were suppressed maximally in non-pregnant adult livers when cholesterol concentrations were increased. In contrast, sterol synthesis rates were suppressed only marginally in fetal livers, fetal bodies, placentas, and yolk sacs when cholesterol concentrations were increased. To begin to elucidate the mechanism responsible for the blunted response of sterol synthesis rates in fetal tissues to exogenous cholesterol, the ratio of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) to Insig-1 was measured in these same tissues since the ratio of SCAP to the Insigs can impact SREBP processing. The fetal tissues had anywhere from a 2-to 6-fold greater ratio of SCAP to Insig-1 than did the adult liver, suggesting constitutive processing of the SREBPs. As expected, the level of mature, nuclear SREBP-2 was not different in the fetal tissues with different levels of cholesterol whereas it was different in adult livers. These findings indicate that the suppression of sterol synthesis to exogenous sterol is blunted in developing tissues and the lack of response appears to be mediated at least partly through relative levels of Insigs and SCAR (c) 2007 Elsevier B.V. All rights reserved.
机译:与成人组织相比,发育中的组织(胎儿,胎盘和卵黄囊)对胆固醇的需求更大。在这里,我们将胆固醇诱导的成年肝脏中固醇合成速率的抑制与金叙利亚仓鼠的胎儿肝,胎儿体,胎盘和卵黄囊进行了比较。当胆固醇水平升高时,未怀孕的成年肝脏中的甾醇合成速率被最大程度地抑制。相反,当胆固醇浓度增加时,仅在胎儿的肝脏,胎儿的身体,胎盘和卵黄囊中甾醇的合成率仅被少量抑制。为了阐明造成胎儿组织中固醇合成速率对外源胆固醇反应迟钝的机制,在这些相同的方法中测量了固醇调节元件结合蛋白(SREBP)裂解激活蛋白(SCAP)与Insig-1的比率因为SCAP与Insigs的比例会影响SREBP的处理。胎儿组织中SCAP与Insig-1的比率比成年肝脏高2到6倍,这表明SREBP的组成性加工。正如预期的那样,在具有不同胆固醇水平的胎儿组织中,成熟的核SREBP-2水平没有差异,而在成年肝脏中则有所不同。这些发现表明,在发育中的组织中对外源固醇的固醇合成抑制作用减弱了,并且缺乏反应似乎至少部分是通过Insigs和SCAR的相对水平来介导的(c)2007 Elsevier B.V.保留所有权利。

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