Cholesterol: Revisiting its fluorescent journey on 200th anniversary of Chevruel's "cholesterine"
Cholesterol: Revisiting its fluorescent journey on 200th anniversary of Chevruel's "cholesterine"
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DOI：
10.3233/bsi-170166
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Anand, Deepak
中科院分区：
文献类型：
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作者：
Chaudhuri, Arunima;Anand, Deepak
迈克尔·雪弗瑞尔发现胆固醇是一种来自胆结石的非皂化脂质，这一发现的遗产已经点燃了两个多世纪以来无数人的想象力和研究。在这篇综述中，我们提供了一个简短的编年史的早期历史的胆固醇研究铺平了道路，今天的膜生物学的理解。我们已经讨论了胆固醇的各种荧光类似物的性质和功能，鉴于超高灵敏度，快速响应和空间分辨率，使用荧光光谱，显微镜和流式细胞术技术。用于胆固醇研究的荧光类似物包括天然存在的类似物（脱氢麦角固醇和胆甾三烯醇）;极性敏感探针（NBD-和丹磺酰-胆固醇）;明亮且光稳定的探针（BODIPY-胆固醇）;可点击的炔胆固醇和胆固醇结合大分子（荧光标记的产气荚膜梭菌溶素O和菲律宾毒素的无毒亚基），用于监测活细胞和固定细胞中的胆固醇含量。本文以动脉粥样硬化、尼曼-匹克C和阿尔茨海默病为代表，阐述了胆固醇荧光类似物在临床研究中的应用。胆固醇的荧光探针的适用性已经变得更加相关的各种超分辨率显微技术的出现今天，并持有的承诺，脱落光到分子管弦乐队的脂质-蛋白质相互作用与纳米级的分辨率。
The legacy of Micheal Chevruel's discovery of "cholesterine" as a non-saponifiable lipid from gall stones has ignited the imagination and research of countless minds for over two centuries now. In this review, we have provided a brief chronicle of the early history of cholesterol research which paved the way to present day understanding of membrane biology. We have discussed the properties and functionality of various fluorescent analogs of cholesterol in view of the ultra-high sensitivity, rapid response and spatial resolution obtained using fluorescence spectroscopic, microscopic and flow cytometric techniques. The repertoire of fluorescent analogs discussed for cholesterol research include the naturally occurring analogs (dehydroergosterol and cholestatrienol); polarity sensitive probes (NBD-and dansyl-cholesterol); bright and photostable probe (BODIPY-cholesterol); clickable alkyne cholesterol and cholesterol binding macromolecules (fluorescently labeled non-toxic subunits of perfringolysin O and filipin) in monitoring cholesterol content in live and fixed cells. We have elaborated on the applications of the fluorescent analogs of cholesterol in clinical research, taking atherosclerosis, Niemann-Pick C and Alzheimer's disease as representative examples. The applicability of fluorescent probes of cholesterol has become more relevant with the advent of various super-resolution microscopic techniques today and holds the promise of shedding light into the molecular orchestra of lipid-protein interaction with nanometer-scale resolution.