Differential effects of cholesterol and its immediate biosynthetic precursors on membrane organization
Differential effects of cholesterol and its immediate biosynthetic precursors on membrane organization
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DOI：
10.1021/bi8001677
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发表时间：
2008-05-20
期刊：
影响因子：
2.9
通讯作者：
Chattopadhyay, Amitabha
中科院分区：
文献类型：
--
作者：
Shrivastava, Sandeep;Paila, Yamuna Devi;Chattopadhyay, Amitabha
胆固醇是脊椎动物细胞膜中最具代表性的甾醇，是长时间、多步骤的甾醇生物合成途径的最终产物。7-脱氢胆固醇-(7-DHC)和Desmosterol是Kandutsch-Russell和Bloch途径中胆固醇的直接生物合成前体。在这篇文章中，我们监测了胆固醇及其两种直接生物合成前体对液体膜和凝胶相膜的生物物理和动力学性质的影响。为了实现这一目标，我们使用了荧光膜探针DPH和TMA-DPH，以及疏水探针Py。我们使用这些探针的结果表明，虽然7-DHC和Desmosterol在一个双键上与胆固醇不同，但它们在膜组织和动力学方面表现出不同的效应。重要的是，我们发现在大多数情况下，胆固醇和Desmosterol对膜组织和动力学的影响是相似的，而7-DHC的影响是相当不同的。这表明，双键在甾醇中的位置是维持膜秩序和动力学的重要决定因素。这些结果具有相关性，因为据报道，胆固醇前体的积累会导致严重的病理情况。
Cholesterol is the most representative sterol present in vertebrate membranes and is the end product of the long and multistep sterol biosynthetic pathway. 7-Dehydrocholesterol- (7-DHC) and desmosterol are the immediate biosynthetic precursors of cholesterol in the Kandutsch-Russell and Bloch pathway. In this article, we have monitored the effect of cholesterol and its two immediate biosynthetic precursors on biophysical and dynamic properties of fluid and gel phase membranes. Toward this goal, we have used fluorescent membrane probes, DPH and TMA-DPH, and the hydrophobic probe, pyrene. Our results using these probes show that although both 7-DHC and desmosterol differ with cholesterol in one double bond, they exhibit differential effects on membrane organization and dynamics. Importantly, we show that the effect of cholesterol and desmosterol on membrane organization and dynamics is similar in most cases, while 7-DHC has a considerably different effect. This demonstrates that the position of the double bond in sterols is an important determinant in maintaining membrane order and dynamics. These results assume relevance since the accumulation of cholesterol precursors have been reported to result in severe pathological conditions.