Albumin and multiple sclerosis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the blood–brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth

NMR Study of the Interaction of Platinum Salts with a Tetrapeptide Containing Cysteinyl Residues

1H-, 13C- and 195Pt-NMR spectroscopies are used to identify the complexes formed between the platinum salts cis-(NH3)2PtCl2 (cis-DDP), trans-(NH3)2PtCl2 (trans-DDP), cis-(en)Pt(ONO2)2, and [(dien)PtBr]Br and the tetrapeptide Boc-Cys1(SMe)-Ser2-Ala3-Cys4(SMe)-CONH2 (CSAC) containing the sequence Cys-X-Y-Cys (X, Y = amino acids) and being a model of metallothionein (MT) and/or a model for platinum binding to methionine type sulfur, known to occur in biological systems. MT, rich in cysteine is known to bind both in vivo and in vitro with the antitumor drug cis-DDP. The 1H- and 13C-NMR assignments were made by two-dimensional homoand heteronuclear experiments for the ligand CSAC. The S-CH3 groups coordinate through sulfur to Pt(II) in all cases. The results show that cis-DDP forms a mixture of different diastereoisomers around the sulfur chiral centers and/or polymeric species with NH3 liberation, due to the strong trans-effect of sulfur. cis-Pt(en)(ONO2)2 forms a monomeric (1:1) chelate structure with CSAC, without en liberation, coordinated through both sulfur atoms. However, slow en liberation could take also place upon increasing temperature. Three signals are observed in the 1H- and 195Pt-NMR spectra of this complex in accordance with the proposed monomeric structure. trans-DDP, on the other hand, forms a 2:1 complex with CSAC identical to the one formed by [Pt(dien)Br]Br, both coordinated to the -S-CH3 groups. No amine release was observed in the case of these two complexes. © 1994, American Chemical Society. All rights reserved