A Small Molecule Fluorogenic Probe for the Detection of Sphingosine in Living Cells,Journal of the American Chemical Society

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A Small Molecule Fluorogenic Probe for the Detection of Sphingosine in Living Cells
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-10-12 , DOI: 10.1021/jacs.0c06652
Andrew K Rudd ₁ , Neel Mittal ₁ , Esther W Lim ₂ , Christian M Metallo ₂ , Neal K Devaraj ₁

Affiliation

The single-chained sphingolipid sphingosine is an essential structural lipid and signaling molecule. Abnormal sphingosine metabolism is observed in several diseases, including cancer, diabetes, and Alzheimer's. Despite its biological importance, there is a lack of tools for detecting sphingosine in living cells. This is likely due to the broader challenge of developing highly selective and live-cell compatible affinity probes for hydrophobic lipid species. In this work, we have developed a small molecule fluorescent turn-on probe for labeling sphingosine in living cells. We demonstrate that this probe exhibits a dose-dependent response to sphingosine and is able to detect endogenous pools of sphingosine. Using our probe, we successfully detected sphingosine accumulation in cells from patients with Niemann-Pick type C1 (NPC1), a lipid transport disorder in which increased sphingosine mediates disease progression. This work provides a simple and accessible method for the detection of sphingosine and should facilitate study of this critical signaling lipid in biology and disease.

中文翻译：

一种用于检测活细胞中鞘氨醇的小分子荧光探针

单链鞘脂鞘氨醇是一种重要的结构脂质和信号分子。在几种疾病中观察到异常的鞘氨醇代谢，包括癌症、糖尿病和阿尔茨海默氏症。尽管具有生物学重要性，但缺乏检测活细胞中鞘氨醇的工具。这可能是由于开发用于疏水脂质物种的高选择性和活细胞相容的亲和探针的更广泛的挑战。在这项工作中，我们开发了一种小分子荧光开启探针，用于标记活细胞中的鞘氨醇。我们证明该探针表现出对鞘氨醇的剂量依赖性反应，并且能够检测内源性鞘氨醇池。使用我们的探针，我们成功地检测到 Niemann-Pick C1 型 (NPC1) 患者细胞中的鞘氨醇积累，一种脂质转运障碍，其中增加的鞘氨醇介导疾病进展。这项工作为检测鞘氨醇提供了一种简单且易于使用的方法，并应有助于研究这种在生物学和疾病中的关键信号脂质。

更新日期：2020-10-12

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