出版社：American Society for Biochemistry and Molecular Biology
摘要：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
