Peptide repertoire of human cerebrospinal fluid: novel proteolytic fragments of neuroendocrine proteins.
Polypeptides in human cerebrospinal fluid (CSF), isolated by phase separation in chloroform-methanol-water and reversed-phase HPLC, were characterised by sequence analysis and mass spectrometry. This identified the presence of peptide fragments of testican, neuroendocrine specific protein VGF, neuroendocrine protein 7B2, chromogranin B/secretogranin I, chromogranin A, osteopontin, IGF-II E-peptide and proenkephalin. The majority of these fragments were generated by proteolysis at dibasic sites, suggesting that they are derived by activities related to prohormone convertase(s). Several of the fragments have previously not been detected, and their functions in CSF or elsewhere are unknown. A characteristic feature of all these fragments is a very high content of acidic residues, in particular glutamic acid. In addition to the fragments of neuroendocrine proteins, endothelin-binding receptor-like protein 2, ribonuclease 1, IGF-binding protein 6, albumin, alpha1-acid glycoprotein 1, prostaglandin-H2 D-isomerase, apolipoprotein A1, transthyretin, beta2-microglobulin, ubiquitin, fibrinopeptide A, and C4A anaphylatoxin were found.
Stark
M
M
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Danielsson
O
O
Griffiths
W J
WJ
Jörnvall
H
H
Johansson
J
J
D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis; D004586:Electrophoresis / Q000379:methods; D004745:Enkephalins / Q000032:analysis; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D013058:Mass Spectrometry / Q000379:methods; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*; D051859:Neuroendocrine Secretory Protein 7B2; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D053495:Osteopontin; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010447:Peptide Hydrolases / Q000378:metabolism; D010907:Pituitary Hormones / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D011506:Proteins / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis
D053379:Chromogranin A; D002864:Chromogranins; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009479:Neuropeptides; D010446:Peptide Fragments; D010907:Pituitary Hormones; D011498:Protein Precursors; D011506:Proteins; D011509:Proteoglycans; C081781:RTN1 protein, human; C497678:SCG5 protein, human; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C504372:Spock1 protein, rat; C506897:Spp1 protein, rat; C029992:proenkephalin; D053495:Osteopontin; D007335:Insulin-Like Growth Factor II; D010447:Peptide Hydrolases