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首页> 外文期刊>Biochemistry >Trans Fatty Acid Derived Phospholipids Show Increased Membrane Cholesterol and Reduced Receptor Activation as Compared to Their Cis Analogs
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Trans Fatty Acid Derived Phospholipids Show Increased Membrane Cholesterol and Reduced Receptor Activation as Compared to Their Cis Analogs

机译:反式脂肪酸衍生的磷脂显示与其顺式类似物相比,膜胆固醇和降低的受体活化

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摘要

The consumption of trans fatty acid(TFA)is linked to the elevation of LDL cholesterol and is considered to be a major health risk factor for coronary heart disease.Despite several decades of extensive research on this subject,the underlying mechanism of how TFA modulates serum cholesterol levels remains elusive.In this study,we examined the molecular interaction of TFA-derived phospholipid with cholesterol and the membrane receptor rhodopsin in model membranes.Rhodopsin is a prototypical member of the G-protein coupled receptor family.It has a well-characterized structure and function and serves as a model membrane receptor in this study.Phospholipid-cholesterol affinity was quantified by measuring cholesterol partition coefficients.Phospholipid-receptor interactions were probed by measuring the level of rhodopsin activation.Our study shows that phospholipid derived from TFA had a higher membrane cholesterol affinity than their cis analogues.TFA phospholipid membranes also exhibited a higher acyl chain packing order,which was indicated by the lower acyl chain packing free volume as determined by DPH fluorescence and the higher transition temperature for rhodopsin thermal denaturation.The level of rhodopsin activation was diminished in TFA phospholipids.Since membrane cholesterol level and membrane receptors are involved in the regulation of cholesterol homeostasis,the combination of higher cholesterol content and reduced receptor activation associated with the presence of TFA-phospholipid could be factors contributing to the elevation of LDL cholesterol.
机译:反式脂肪酸(TFA)的消耗与LDL胆固醇的升高有关,被认为是冠心病的主要健康危险因素。分别对该主题的几十年进行广泛研究,TFA如何调节血清的潜在机制胆固醇水平仍然难以捉摸。在本研究中,我们研究了TFA衍生的磷脂与胆固醇的分子相互作用和模型膜中的膜受体罗二元蛋白。Hehodopsin是G-蛋白偶联受体家庭的原型构件。具有良好的特征结构和功能并用作本研究中的模型膜受体。通过测量胆固醇分配系数来定量磷脂 - 胆固醇亲和力。通过测量罗多蛋白酶活化水平来探讨磷脂 - 受体相互作用。研究表明,来自TFA的磷脂具有A.比它们的顺式类似物更高的膜胆固醇亲和力。磷脂膜也表现出a通过DPH荧光测定的下酰基链填充量和逆转温度的较低酰基链填充量表示,罗多双石热变性的较高转变温度表示。在TFA磷脂中罗多蛋白酶活化水平降低。胰膜胆固醇水平和膜受体在参与调节胆固醇稳态,胆固醇含量的组合和与TFA-磷脂的存在相关的受体激活可能是有助于LDL胆固醇升高的因素。

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  • 来源
    《Biochemistry》 |2005年第11期|共8页
  • 作者单位

    Section of Fluorescence Studies Laboratory of Membrane Biochemistry and Biophysics National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Rockville Maryland 20852;

    Section of Fluorescence Studies Laboratory of Membrane Biochemistry and Biophysics National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Rockville Maryland 20852;

    Section of Fluorescence Studies Laboratory of Membrane Biochemistry and Biophysics National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Rockville Maryland 20852;

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  • 正文语种 eng
  • 中图分类 生物化学;
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