J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.C400005-JLR200 on December 1, 2004

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
C400005-JLR200v1
46/2/191    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leoni, V.
Right arrow Articles by Masterman, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leoni, V.
Right arrow Articles by Masterman, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 46, 191-195, February 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Rapid Communication

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

Valerio Leoni*, Dieter Lütjohann1,{dagger} and Thomas Masterman§

* Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital in Huddinge, Stockholm, Sweden
{dagger} Department of Clinical Pharmacology, University of Bonn, Bonn, Germany
§ Division of Neurology, NEUROTEC, Karolinska Institutet, Stockholm, Sweden

1 To whom correspondence should be addressed. e-mail: dieter.luetjohann{at}ukb.uni-bonn.de


ABSTRACT

In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Häke, S. Meier, C. S. Raine, R. Nitsch, F. Zipp, and O. Ullrich. 2003. Activation of microglial poly (ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J. Exp. Med. 198: 1729–1740], extremely high levels of 7-oxocholesterol were reported in cerebrospinal fluid (CSF) of 11 patients with multiple sclerosis (MS) [7.4 ± 0.3 mg/l (mean ± SEM)]. The corresponding level of 12 subjects with other kinds of neurological diseases was reported to be 0.5 ± 0.1 mg/l. Such high levels of 7-oxocholesterol were found to cause neuronal damage of living brain tissues. Using a highly accurate method for an assay of 7-oxocholesterol based on isotope dilution-mass spectrometry and anaerobic conditions during workup, we found that the level of 7-oxocholesterol in CSF from 29 Swedish patients with MS was only 1.2 µg/l (median, ranging from 0.4 to 4.6 µg/l), less than 1/1,000th of the previously reported level. The level of 7-oxocholesterol in CSF from 24 Swedish control patients was 0.9 µg/l (0.3–2.3 µg/l), slightly but significantly lower than the CSF level in MS patients (P = 0.002). In vitro-induced lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7-oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to ~0.3 mg/l.

These 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.

Abbreviations: ABAP, 2,2'-azobis-2-amidinopropane hydrochloride; BHT, 3,5-di-tert-butyl-4-hydroxytoluene; CSF, cerebrospinal fluid; ID-MS, isotope dilution-mass spectrometry; MS, multiple sclerosis; 24OHC, 24S-hydroxycholesterol; 27OHC, 27-hydroxycholesterol; SIM, selected ion monitoring; TMSi, trimethylsilyl

Supplementary key words 27-hydroxycholesterol • 24S-hydroxycholesterol • neurological disease • lipid peroxidation • oxysterols


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.