NDLI: Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

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Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

Content Provider	Springer Nature Link
Author	Xu, Libin Kliman, Michal Forsythe, Jay G. Korade, Zeljka Hmelo, Anthony B. Porter, Ned A. McLean, John A.
Copyright Year	2015
Abstract	Profiling and imaging of cholesterol and its precursors by mass spectrometry (MS) are important in a number of cholesterol biosynthesis disorders, such as in Smith-Lemli-Opitz syndrome (SLOS), where 7-dehydrocholesterol (7-DHC) is accumulated in affected individuals. SLOS is caused by defects in the enzyme that reduces 7-DHC to cholesterol. However, analysis of sterols is challenging because these hydrophobic olefins are difficult to ionize for MS detection. We report here sputtered silver matrix-assisted laser desorption/ionization (MALDI)-ion mobility-MS (IM-MS) analysis of cholesterol and 7-DHC. In comparison with liquid-based AgNO$_{3}$ and colloidal Ag nanoparticle (AgNP), sputtered silver NP (10–25 nm) provided the lowest limits-of-detection based on the silver coordinated [cholesterol + Ag]$^{+}$ and [7-DHC + Ag]$^{+}$ signals while minimizing dehydrogenation products ([M + Ag-2H]$^{+}$). When analyzing human fibroblasts that were directly grown on poly-L-lysine-coated ITO glass plates with this technique, in situ, the 7-DHC/cholesterol ratios for both control and SLOS human fibroblasts are readily obtained. The m/z of 491 (specific for [7-DHC + $^{107}$Ag]$^{+}$) and 495 (specific for [cholesterol + $^{109}$Ag]$^{+}$) were subsequently imaged using MALDI-IM-MS. MS images were co-registered with optical images of the cells for metabolic ratio determination. From these comparisons, ratios of 7-DHC/cholesterol for SLOS human fibroblasts are distinctly higher than in control human fibroblasts. Thus, this strategy demonstrates the utility for diagnosing/assaying the severity of cholesterol biosynthesis disorders in vitro.Graphical Abstract
Starting Page	924
Ending Page	933
Page Count	10
File Format	PDF
ISSN	10440305
Journal	Journal of The American Society for Mass Spectrometry
Volume Number	26
Issue Number	6
e-ISSN	18791123
Language	English
Publisher	Springer US
Publisher Date	2015-03-31
Publisher Institution	The American Society for Mass Spectrometry
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Sputter coating Silver Cholesterol 7-Dehydrocholesterol Ion mobility-mass spectrometry Imaging Smith-Lemli-Opitz syndrome Analytical Chemistry Biotechnology Organic Chemistry Proteomics Bioinformatics
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Structural Biology

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Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

Smith-Lemli-Opitz Syndrome

Corpus Callosum in Smith-Lemli-Opitz Syndrome

7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome (Dataset)

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

Interference of 7-dehydrocholesterol in α-tocopherol determination by high-performance liquid chromatography: A possible screening test for the smith-lemli-opitz syndrome

Comparison of the liquid-ordered bilayer phases containing cholesterol or 7-dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz Syndrome

Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

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