Sterol lipidomics in health and disease: Methodologies and applications

Griffiths, William J.; Wang, Yuqin

doi:10.1002/ejlt.200800116

Cited by 23 publications

(8 citation statements)

References 175 publications

(242 reference statements)

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“…Clearly the composition of the population can and will play a role in the measured levels of various compounds. This being written, the values we report for the Cooper Institute cohort compare favorably with other values in the literature ( 27 ), with the understanding that there can be variation between populations.…”

Section: Quality Analysis/quality Controlsupporting

confidence: 65%

“…We assayed for approximately 60 compounds, but only a subset of 22 compounds was routinely detected. Not included in these data are values obtained for most known oxidation products, such as the 5/6( ␣ / ␤ )-epoxycholesterols ( 27 ), due in part to problems with the primary standard or deuterated analog, which have been subsequently resolved. Table 2 provides values for 25-hydroxyvitamin D 3 and a select group of sterols and oxysterols measured in the 200 samples.…”

Section: Datamentioning

confidence: 99%

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A comprehensive method for extraction and quantitative analysis of sterols and secosteroids from human plasma

McDonald

Smith

Stiles

et al. 2012

Journal of Lipid Research

203

187

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are integral building blocks in the cellular membranes of animals and have important functions in signaling, regulation, and metabolism ( 1 ). To date, the majority of studies have focused on cholesterol, the most abundant sterol in mammals that serves as both a precursor and product to a host of important molecules, including steroid hormones, bile acids, oxysterols, and intermediates in the cholesterol biosynthetic pathway ( 2-4 ). Although cholesterol has gained signifi cant notoriety due to the compound's negative impact on health, other sterols, such as plant-derived phytosterols, are thought to offer potential human health benefi ts by lowering circulating cholesterol levels ( 5, 6 ).Novel functions for sterols and secosteroids continue to be identifi ed. For example, the cholesterol metabolites 25-hydroxycholesterol and 7 ␣ ,25-dihydroxycholesterol have recently been shown to play important signaling roles in the immune system ( 7-9 ). 24-hydroxycholesterol has been shown to be involved in cholesterol turnover in the brain, and it plays a role in memory ( 10 ) and glucose metabolism ( 11 ). Alterations in vitamin D levels arising from the lack of sun exposure and/or use of sunscreen are postulated to have a negative impact on health ( 12, 13 ). These fi ndings together with the large number of sterols suggest that there may be undiscovered roles for sterols in biology, and they highlight the need for continued research into the biochemical pathways associated with these compounds.The extraction and analysis of sterols in human plasma present a unique challenge due to their virtual insolubility, sequestration within lipoproteins, and dramatic differences in the levels of individual sterols. Cholesterol is the most abundant sterol, with circulating levels on the order of 1 to 3 mg/ml, whereas 25-hydroxycholesterol is a millionfold less abundant at 1 to 3 ng/ml ( 14, 15 ). The circulating form of sterols in humans is primarily as steryl esters, in which a fatty acid is esterifi ed to carbon 3 of the sterol; Abstract We describe the development of a method for the extraction and analysis of 62 sterols, oxysterols, and secosteroids from human plasma using a combination of HPLC-MS and GC-MS. Deuterated standards are added to 200 l of human plasma. Bulk lipids are extracted with methanol:dichloromethane, the sample is hydrolyzed using a novel procedure, and sterols and secosteroids are isolated using solid-phase extraction (SPE). Compounds are resolved on C 18 core-shell HPLC columns and by GC. Sterols and oxysterols are measured using triple quadrupole mass spectrometers, and lathosterol is measured using GC-MS. Detection for each compound measured by HPLC-MS was ʜ 1 ng/ml of plasma. Extraction effi ciency was between 85 and 110%; day-to-day variability showed a relative standard error of <10%. Numerous oxysterols were detected, including the side chain oxysterols 22-, 24-, 25-, and 27-hydroxycholesterol, as well as ring-structure oxysterols 7 ␣ -and 4 ␤ -hydroxycholesterol. Intermediates from the cholesterol b...

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Section: Quality Analysis/quality Controlsupporting

confidence: 65%

Section: Datamentioning

confidence: 99%

A comprehensive method for extraction and quantitative analysis of sterols and secosteroids from human plasma

McDonald

Smith

Stiles

et al. 2012

Journal of Lipid Research

203

187

View full text Add to dashboard Cite

show abstract

“…As in adult mouse brain ( 9,21,24,25,35 ), the most-abundant monohydroxycholesterol found in newborn mouse brain is 24S-hydroxycholesterol ( Fig. 1 ; supplementary Table II, see also supplementary Table II in ( 25 ) and Table III in ( 36 ) for published data on adult mouse). Once GP chargetagged, this oxysterol gives an [M] + ion of m/z 534.4054.…”

Section: Oxysterols In Newborn Mouse Brainmentioning

confidence: 97%

Analysis of bioactive oxysterols in newborn mouse brain by LC/MS

Meljon¹,

Theofilopoulos

Shackleton³

et al. 2012

Journal of Lipid Research

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“…A first-pass screen using the PTAD protocol identifies an initial lead-hit list, which can then be verified by the use of established analytical methods to provide a more complete sterol profile. These established methods (35,36) consume more instrument time making them less amenable for use with high throughput screening. It should be noted that the experimental conditions of the screening procedures do involve the use of a medium with a known quantity of Chol, a known component of serum.…”

Section: High-throughput Screening For Compounds That Target Chol Biomentioning

confidence: 99%

Identification and characterization of prescription drugs that change levels of 7-dehydrocholesterol and desmosterol

Wages

Kim

Korade

et al. 2018

Journal of Lipid Research

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Regulating blood cholesterol (Chol) levels by pharmacotherapy has successfully improved cardiovascular health. There is growing interest in the role of Chol precursors in the treatment of diseases. One sterol precursor, desmosterol (Des), is a potential pharmacological target for inflammatory and neurodegenerative disorders. However, elevating levels of the precursor 7-dehydrocholesterol (7-DHC) by inhibiting the enzyme 7-dehydrocholesterol reductase is linked to teratogenic outcomes. Thus, altering the sterol profile may either increase risk toward an adverse outcome or confer therapeutic benefit depending on the metabolite affected by the pharmacophore. In order to characterize any unknown activity of drugs on Chol biosynthesis, a chemical library of Food and Drug Administration-approved drugs was screened for the potential to modulate 7-DHC or Des levels in a neural cell line. Over 20% of the collection was shown to impact Chol biosynthesis, including 75 compounds that alter 7-DHC levels and 49 that modulate Des levels. Evidence is provided that three tyrosine kinase inhibitors, imatinib, ponatinib, and masitinib, elevate Des levels as well as other substrates of 24-dehydrocholesterol reductase, the enzyme responsible for converting Des to Chol. Additionally, the mechanism of action for ponatinib and masitinib was explored, demonstrating that protein levels are decreased as a result of treatment with these drugs.

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Sterol lipidomics in health and disease: Methodologies and applications

Cited by 23 publications

References 175 publications

A comprehensive method for extraction and quantitative analysis of sterols and secosteroids from human plasma

A comprehensive method for extraction and quantitative analysis of sterols and secosteroids from human plasma

Analysis of bioactive oxysterols in newborn mouse brain by LC/MS

Identification and characterization of prescription drugs that change levels of 7-dehydrocholesterol and desmosterol

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