Origin and Content of Cholesterol Oxidation Products in Biological Samples

Diczfalusy, Ulf; Guardiola, Francesc; Dutta, Paresh C.; Codony, R.; Savage, Geoffrey P.

doi:10.1201/9781439822210.ch12

Cited by 22 publications

(33 citation statements)

References 145 publications

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“…The levels of 7-oxygenated steroids reported in plasma have been markedly decreased during the last two decades in parallel with the development of more accurate methodologies (13). The levels of 7-oxocholesterol in human plasma have been reported to vary by a factor of almost 200 in some previous publications (14).…”

Section: Discussionmentioning

confidence: 85%

Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis

Leoni

Lütjohann

Masterman

2005

Journal of Lipid Research

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1), high levels of the cholesterol oxidation product 7-oxocholesterol were reported in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS): ‫ف‬ 7 mg/l. Unsurprisingly, such high levels were found to cause neuronal damage under in vitro conditions. The levels were considerably lower in CSF from control subjects: ‫ف‬ 0.5 mg/l. In a previous work from this laboratory, we measured levels of 7-oxygenated oxysterols in CSF from different groups of patients (2), and the levels were always found to be less than 0.01 mg/l (our unpublished observation). It is well established that the other oxysterols in CSF, 24 S -hydroxycholesterol (24OHC) and 27-hydroxycholesterol (27OHC), are present in similarly low concentrations (3-6). In view of this, and in view of the suggestion by Diestel et al.(1) that 7-oxocholesterol could be an important link between demyelination and neuronal damage, we measured the levels of 7-oxocholesterol in CSF from 29 Swedish patients with MS and 24 control subjects. A highly accurate and sensitive method was used based on isotope dilution-mass spectrometry (ID-MS) using deuterium-labeled internal oxysterol standards. The results are discussed in relation to the fact that 7-oxygenated steroids are easily artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples.

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Section: Discussionmentioning

confidence: 85%

Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis

Leoni

Lütjohann

Masterman

2005

Journal of Lipid Research

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“…Oxysterols are present in tissues with a large excess of cholesterol, creating a ratio of cholesterol to oxysterol that ranges from 10 3 to 10 6 (25). Such a large concentration disparity might be expected to reduce the effectiveness of SULT2B1b in being able to sulfonate 7-KC added to culture medium at only 5 nM, which when taken up by the 293T and MCF-7 cells would have to compete with the large excess of endogenous cholesterol; however, this turned out not to be the case.…”

Section: Discussionmentioning

confidence: 99%

Oxysterols are substrates for cholesterol sulfotransferase

Fuda

Javitt

Mitamura

et al. 2007

Journal of Lipid Research

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Oxysterols constitute a class of cholesterol derivatives that exhibit broad biological effects ranging from cytotoxicity to regulation of nuclear receptors. The role of oxysterols such as 7-ketocholesterol (7-KC) in the development of retinal macular degeneration and atheromatous lesions is of particular interest, but little is known of their metabolic fate. We establish that the steroid/sterol sulfotransferase SULT2B1b, known to efficiently sulfonate cholesterol, also effectively sulfonates a variety of oxysterols, including 7-KC. The cytotoxic effect of 7-KC on 293T cells was attenuated when these cells, which do not express SULT2B1b, were transfected with SULT2B1b cDNA. Importantly, protection from 7-KC-induced loss of cell viability with transfection correlated with the synthesis of SULT2B1b protein and the production of the 7-KC sulfoconjugate (7-KCS). Moreover, when 7-KCS was added to the culture medium of 293T cells in amounts equimolar to 7-KC, no loss of cell viability occurred. Additionally, MCF-7 cells, which highly express SULT2B1b, were significantly more resistant to the cytotoxic effect of 7-KC. We extended the range of oxysterol substrates for SULT2B1b to include 7a/ 7b-hydroxycholesterol and 5a,6a/5b,6b-epoxycholesterol as well as the 7a-hydroperoxide derivative of cholesterol. Thus, SULT2B1b, by acting on a variety of oxysterols, offers a potential pathway for modulating in vivo the injurious effects of these compounds.-Fuda, H., N. B. Javitt, K. Mitamura, S. Ikegawa, and C. A. Strott. Oxysterols are substrates for cholesterol sulfotransferase. J. Lipid Res.

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“…attention as diagnostic biomarkers of oxidative stress, as intermediates in bile acid biosynthesis and messengers for cell signaling and cholesterol transport 15 . The free radicalmed i a t e d o x i d a tion of cholesterol gives 7 α-a n d 7β-hydroperoxycholesterol 7α-OOHCh and 7β-OOHCh , 5α, 6α, 5β, and 6β-epoxycholesterol, and 7-ketocholesterol 7-KCh , as the major products 16 .…”

Section: Enzymatic and Non-enzymatic Lipid Peroxidationmentioning

confidence: 99%