Metabonomics Study of Brain-Specific Human S100B Transgenic Mice by Using High-Performance Liquid Chromatography Coupled with Quadrupole Time of Flight Mass Spectrometry

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders that occur in the elderly. Until now, the cause and mechanism of PD are unknown, making further studies necessary. S100B is a member of a group of Ca 2ϩ -binding protein mostly astrocytederived factor that has been shown to be involved in the maintenance and stimulation of neurons and glia cells by regulating a variety of cellular mechanisms such as proliferation, differentiation and energy metabolism. Increased levels of S100B were detected in the serum of the patients of PD.1,2) The expression of S100B in the substantia nigra and striatum of mice has a close relationship with a decreased number of dopaminergic neurons after injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the abdominal cavity of mice.3) We conclude that S100B has a close relationship with the development of PD, but are still unsure of a concrete mechanism. To reveal the effects of over-expression of S100B on the metabonomics of endogenous components in the brain is very helpful to investigate the mechanism of S100B in the development of PD.Metabonomics, defined as "the quantitative measurement of the dynamic multiparametric metabolic response of living organism to pathophysiological stimulation or genetic modification," 4) combined with multivariate analysis, has been extensively applied to many fields, such as understanding the biochemical basis of diseases, drug toxicity and diagnosis, and treatment of diseases according to the global metabolic profiles in biological fluids (serum, plasma, urine) and tissues.5-8) Metabonomics study was divided into four levels, including target analysis, profiling analysis, fingerprint analysis and metabonomics analysis. In this paper, metabonomics study based on the HPLC/MS-ESI-TOF analysis was applied to understanding the metabolic profiling of S100B transgenic mice and identifying the potential biomarkers relating to S100B protein.Besides of high-field proton nuclear magnetic resonance (NMR) spectroscopy, high-performance liquid chromatography (HPLC) coupled with MS has been widely applied for metabolic profiles of biological samples and reversed-phase (RP) chromatography is the most commonly used separation technique. Although it is impossible to determine the individual level of every single endogenous metabolite in a biofluid, to obtain a metabolic fingerprint, preferably as many metabolites as possible, should be detected. It was found that the most polar components in biological samples would not have been retained on the RP chromatography column, and could not be detected. Hydrophilic interaction liquid chromatography (HILIC) is a complementary method to RP chromatography. HILIC is similar to normal phase chromatography and the separation is based on the distribution between stationary and mobile phases, although it differs with RP chromatography in that aqueous mobile phases can be used. 9)In this paper, with the aim of increasing the number of metabolites to be detected, RP-LC and HILIC were combined. ...

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