15-Oxygenated cholesterol species such as 5 α-cholest-8(14)ene-3 β ,15 α -diol (15HC) and 3 β -hydroxy-5 α-cholest-8(14)- en-15-one (15KC) are commercially available synthetic products unlikely to occur in biological systems. Surprisingly, Farez et al. recently reported that these two steroids occur in human circulation at levels considerably higher than those of any other endogenous oxysterol [Farez, M. et al. 2009. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinfl ammation in progressive EAE. Nat. Immunol. 10: 958-964]. The levels were reported to be increased in patients with multiple sclerosis in a progressive phase and the authors suggested that this could be utilized diagnostically. Based on extensive in vitro experiments exposing cells to the same high levels of 15HC as found in vivo (1000 ng/ml) the authors concluded that 15HC may be an important pathogenetic factor in multiple sclerosis. Using combined gas chromatography-mass spectrometry we fail to detect signifi-cant plasma levels of 15HC either in healthy controls or in patients with multiple sclerosis (levels < 2 ng/ml). If 15KC is present in these plasma samples, the concentration of it must be <10 ng/ml. Our failure to detect signifi cant levels of the above steroids could not be due to loss during hydrolysis and work-up because recovery of the added two oxysterols was close to 100%. Autoxidation of lipoprotein-bound cholesterol resulted in extensive conversion of cholesterol into 7-oxygenated but not 15-oxygenated sterols. We conclude that if present there are trace amounts only of the above 15-oxygenated steroids in human circulation and that the role of such oxysterols as pathogenetic factors and biomarkers must be reconsidered. -Björkhem, I., A. Lövgren- Sandblom, F. Piehl, M. Khademi, H. Pettersson, V. Leoni, T. Olsson, and U. Diczfalusy. High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: fact or fiction?

Björkhem, I., Lövgren-Sandblom, A., Piehl, F., Khademi, M., Pettersson, H., Leoni, V., et al. (2011). High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: Fact or fi ction?. JOURNAL OF LIPID RESEARCH, 52(1), 170-174 [10.1194/jlr.D011072].

High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: Fact or fi ction?

Leoni, V;
2011

Abstract

15-Oxygenated cholesterol species such as 5 α-cholest-8(14)ene-3 β ,15 α -diol (15HC) and 3 β -hydroxy-5 α-cholest-8(14)- en-15-one (15KC) are commercially available synthetic products unlikely to occur in biological systems. Surprisingly, Farez et al. recently reported that these two steroids occur in human circulation at levels considerably higher than those of any other endogenous oxysterol [Farez, M. et al. 2009. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinfl ammation in progressive EAE. Nat. Immunol. 10: 958-964]. The levels were reported to be increased in patients with multiple sclerosis in a progressive phase and the authors suggested that this could be utilized diagnostically. Based on extensive in vitro experiments exposing cells to the same high levels of 15HC as found in vivo (1000 ng/ml) the authors concluded that 15HC may be an important pathogenetic factor in multiple sclerosis. Using combined gas chromatography-mass spectrometry we fail to detect signifi-cant plasma levels of 15HC either in healthy controls or in patients with multiple sclerosis (levels < 2 ng/ml). If 15KC is present in these plasma samples, the concentration of it must be <10 ng/ml. Our failure to detect signifi cant levels of the above steroids could not be due to loss during hydrolysis and work-up because recovery of the added two oxysterols was close to 100%. Autoxidation of lipoprotein-bound cholesterol resulted in extensive conversion of cholesterol into 7-oxygenated but not 15-oxygenated sterols. We conclude that if present there are trace amounts only of the above 15-oxygenated steroids in human circulation and that the role of such oxysterols as pathogenetic factors and biomarkers must be reconsidered. -Björkhem, I., A. Lövgren- Sandblom, F. Piehl, M. Khademi, H. Pettersson, V. Leoni, T. Olsson, and U. Diczfalusy. High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: fact or fiction?
Articolo in rivista - Articolo scientifico
3 β -hydroxy-5 α -cholest-8(14)-en-15-one; 5 α -cholest-8(14)ene-3 β 15 α-diol; Autoxidation; Oxysterols;
English
7-ott-2010
2011
52
1
170
174
open
Björkhem, I., Lövgren-Sandblom, A., Piehl, F., Khademi, M., Pettersson, H., Leoni, V., et al. (2011). High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: Fact or fi ction?. JOURNAL OF LIPID RESEARCH, 52(1), 170-174 [10.1194/jlr.D011072].
File in questo prodotto:
File Dimensione Formato  
Björkhem-2011-Journal of Lipid Research-VoR.pdf

accesso aperto

Descrizione: CC BY 4.0
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Creative Commons
Dimensione 550.64 kB
Formato Adobe PDF
550.64 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/221843
Citazioni
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 18
Social impact