期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 142, 期 42, 页码 17887-17891出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c06652
关键词
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资金
- National Institute of Health [DP2DK111801, R01 CA234245]
- NIH/NCI though the Ruth L. Kirschstein National Research Service Award [T32 CA009523]
- NIH [T32 EB009380]
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.
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