Proteomic analysis of multiple sclerosis cerebrospinal fluid

Abstract

Two-dimensional gel electrophoresis and peptide mass fingerprinting were used to identify proteins in cerebrospinal fluid (C SF) pooled from three patients with multiple sclerosis (MS) and in C SF pooled from three patients with non-MS inflammatory central nervous system (C NS) disorders. Resolution of C SF proteins on three pH gradients (3-10, 4-7 and 6-11) enabled identification of a total of 430 spots in the MS C SF proteome that represented 61 distinct proteins. The gels containing MS C SF revealed 103 protein spots that were not seen on control gels. A ll but four of these 103 spots were proteins known to be present in normal human C SF. The four exceptio ns were: C RTAC -1B (cartilage acidic protein), tetranectin (a plasminogen-binding protein), SPARC -like protein (a calcium binding cell signalling glycoprotein), and autotaxin t (a phosphodiesterase). It remains unknown whether these four proteins are related to the cause and patho genesis of MS.

Keywords

cerebrospinal fluid multiple sclerosis proteomics

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References

Kurtzke JF. On the time of onset in multiple sclerosis . Acta Neurol Scand 1965; 41: 140-158 .

Kurtzke JF , Hyllested K. Multiple sclerosis in the Faroe Islands: I. Clinical and epidemiological features . Ann Neurol 1979; 5: 6-21 .

Spielman RS , Nathanson N. The genetics of susceptibility to multiple sclerosis . Epidemiol Rev 1982; 4: 45-65 .

Mattson DH , Roos RP , Arnason BGW. Comparison of agar gel electrophoresis and isoelectric focusing in multiple sclerosis and subacute sclerosing panencephalitis . Ann Neurol 1981; 9: 34-41 .

Gilden DH , Devlin ME , Burgoon MP , Owens GP. The search for virus in multiple sclerosis brain . Mult Scler 1996; 2: 179-183 .

Wasinger VC , Cordwell SJ , Cerpa-Poljak A , Yan JX , Gooley AA , Wilkins MR et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium . Electrophoresis 1995; 16: 1090-1094 .

Davidsson P , Paulson L , Hesse C , Blennow K , Nilsson CL. Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two-dimensional electrophoresis approach prior to mass spectrometry . Proteomics 2001; 1: 444-452 .

Davidsson P , Westman-Brinkmalm A , Nilsson CL , Lindbjer M , Paulson L , Andreasen N et al. Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients . Neuroreport 2002; 13: 611-615 .

Yuan X , Russell T , Wood G , Desiderio DM. Analysis of the human lumbar cerebrospinal fluid proteome . Electrophoresis 2002; 23: 1185-1196 .

10.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding . Anal Biochem 1976; 72: 248-254 .

11.

Perkins DN , Pappin DJ , Creasy DM , Cottrell JS. Probability-based protein identification by searching sequence databases using mass spectrometry data . Electrophoresis 1999; 20: 3551-3567 .

12.

Sickmann A , Dormeyer W , Wortelkamp S , Woitalla D , Kuhn W , Meyer H. identification of proteins from human cerebrospinal fluid, separated by two-dimensional polyacrylamide gel electrophoresis . Electrophoresis 2000; 21: 2721-2728 .

13.

Sickmann A , Dormeyer W , Wortelkamp S , Woitalla D , Kuhn W , Meyer HE. Towards a high resolution separation of human cerebrospinal fluid . J Chromatogr B Anal Technol Biomed Life Sci 2002; 771: 167-196 .

14.

Storch MK , Piddlesden S , Haltia M , Iivanainen M , Morgan P , Lassmann H. Multiple sclerosis: in situ evidence for antibody and complement-mediated demyelination . Ann Neurol 1998; 43: 465-471 .

15.

Kim JK , Mastronardi FG , Wood DD , Lubman DM , Zand R , Moscarello MA. Multiple sclerosis: an important role for post-translational modifications of myelin basic protein in pathogenesis . Mol Cell Proteomics 2003; 2: 453-462 .

16.

Yan Q , Sage EH. SPARC, a matricellular glycoprotein with important biological functions . J Histochem Cytochem 1999; 47: 1495-1505 .