Quantitative detection of free 24S-hydroxycholesterol, and 27-hydroxycholesterol from human serum.

Veera Venkata Ratnam Bandaru,Norman J Haughey

doi:10.1186/s12868-014-0137-z

Veera Venkata Ratnam Bandaru, Norman J Haughey

Open Access

https://doi.org/10.1186/s12868-014-0137-z

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Abstract

BackgroundCholesterol metabolism is important for the maintenance of myelin and neuronal membranes in the central nervous system. Blood concentrations of the brain specific cholesterol metabolite 24S-hydroxysterol to the peripheral metabolite 27-hydroxycholesterol may be useful surrogate markers for neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, HIV-Associated Neurocognitive Disorders, and Multiple Sclerosis. However, current methods to isolate hydroxycholesterols are labor intensive, prone to produce variable extraction efficiencies and do not discriminate between free and esterfied forms of hydroxycholesterols. Since free hydroxycholesterols are the biologically active form of these sterols, separating free from esterfied forms may provide a sensitive measure to identify disease-associated differences in brain sterol metabolism.ResultsWe found that average human serum concentrations were 12.3 ± 4.79 ng/ml for free 24(s)-hydroxycholesterol and 17.7 ± 8.5 ng/ml for 27-hydroxycholesterol.ConclusionSerum measurements of these biologically active oxysterols may be useful surrogate measures for brain health in a variety of neurodegenerative conditions.

Highlights

Cholesterol metabolism is important for the maintenance of myelin and neuronal membranes in the central nervous system
Hydroxycholesterols are important for cholesterol transport from the periphery to the liver [2], modulate the expression of sterol sensitive genes involved in lipid and sterol biosynthesis [3,4], act as substrates for the formation of bile salts [5], serve as ligands that activate nuclear liver X receptorsα and -β [6], and are involved in the regulation of cholesterol and lipid metabolism and homeostasis [7,8]
Hydroxycholesterols were identified -as ammonium adducts of 24S-hydroxycholesterol and 27hydroxycholesterol or 24(R/S)-hydroxycholesterol (d6) using ESI/MS operated in the positive ion mode

Summary

Introduction

Cholesterol metabolism is important for the maintenance of myelin and neuronal membranes in the central nervous system. In the central nervous system, hydroxycholesterols regulate arachidonic acid release, voltage-gated calcium channels, synaptic plasticity, induce IL-8, promote neurogenesis and induce apoptosis [9,10,11,12,13,14,15,16]. Consistent with these important roles for regulating biological functions, levels of free hydroxycholesterols are extremely low and tightly controlled, with the majority of hydroxycholesterols maintained in esterified forms [17,18]

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