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Results for “Myelin Basic Protein”

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PubMed1986

In vitro carboxymethylation of myelin basic protein.

During a study to find natural substrate proteins of carboxymethylation, myelin basic protein was found to be a good substrate. The two protein carboxymethylases were purified partially using myelin basic protein as a substrate. These two enzymes may be identical with protein carboxymethylase I and II, which have been found to methylate gamma-globulin. The Km of myelin basic protein (25 microM) was very small compared with other substrates. The activities of the two carboxymethylases were high in the rat brain in comparison to the other rat organs. The activity increased during the period of myelination in the rat brain. These findings suggest that carboxymethylation of myelin basic protein may play an important role in myelination.

Animals↗

PubMed1977

Non-covalent cross-linking of lipid bilayers by myelin basic protein: a possible role in myelin formation.

Myelin basic protein associates with bilayer vesicles of pure egg phosphatidylcholine, L-alpha-dimyristoyl phosphatidylcholine and DL-alpha-dipalmitoyl phosphatidylcholine. Under optimum conditions the vesicles contain 15-18% of protein by weight. The binding to dipalmitoyl phosphatidylcholine is facilitated above its gel-to-liquid crystalline transition temperature. At low ionic strength the protein provokes a large increase in vesicle size and aggregation of these enlarged vesicles. Above a sodium chloride concentration of 0.07 M vesicle fusion is far less marked but aggregation persists. The pH- and ionic strength-dependence of this aggregation follows that of the protein alone; in both cases it occurs despite appreciable electrostatic repulsion between the associated species. A similar interaction was observed with diacyl phosphatidylserine vesicles. These observations, which contrast with earlier reports in the literature of a lack of binding of basic protein to phosphatidylcholine-containing lipids, demonstrate the ability of this protein to interact non-ionically with lipid bilayers. The strong cross-linking of lipid bilayers suggests a role for basic protein in myelin, raising the possibility that the protein is instrumental in collapsing the oligodendrocyte cell membrane and thus initiating myelin formation.

Hydrogen-Ion Concentration↗

PubMed1991

Effects of dexamethasone on the expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein genes in developing rat brain.

Effects of dexamethasone (DEX) on the relative abundance of myelin basic protein (MBP), proteolipid protein (PLP) and glial fibrillary acidic protein (GFAP) mRNAs in the developing rat brain were examined. After DEX (1.0 mg/kg body weight) or saline was administered intraperitoneally to 3-day-old rats for 7 consecutive days, wet weight, DNA content and the relative abundance of the glia-specific mRNAs in cerebrum and cerebellum were analyzed at postnatal days (P) 10, 20 and 30. DEX decreased both wet weight and DNA content in cerebellum more profoundly than in cerebrum. The appearance of MBP, PLP and GFAP mRNAs in cerebellum preceded that in cerebrum in the control group. In cerebrum, the relative abundance of MBP and PLP mRNAs was significantly less in the DEX group than that in the control group at P20 and P30. The relative abundance of the GFAP mRNA was significantly less in the DEX group than in the control group at P10 and P20, but there was no significant difference at P30. In cerebellum, a significant decrease in the abundance of MBP, PLP and GFAP mRNAs in the DEX group was observed only at P10 but not at P20 and P30. Our findings indicate that DEX suppresses expression of genes related to glial functions, especially myelination when administered in the early postnatal period.

Aging↗

PubMed1994

Relative frequency of autoantibodies to myelin basic protein and proteolipid protein in optic neuritis and multiple sclerosis cerebrospinal fluid.

Myelin basic protein (MBP) and proteolipid protein (PLP) were purified from non-MS human brain and used in solid phase radioimmunoassays to detect their specific antibodies in cerebrospinal fluid (CSF) of optic neuritis and clinically definite multiple sclerosis (MS) patients. In 53 optic neuritis patients free anti-MBP was elevated in 47 and in 6 of these 47 patients bound anti-MBP was also increased. The remaining 6 patients with undetectable anti-MBP had increased levels of anti-PLP in their CSF. None of these optic neuritis patients had autoantibodies to both antigens. Of 173 MS patients with acute relapses 169 had increased free anti-MBP. Three of the 4 remaining patients with undetectable anti-MBP had increased anti-PLP in their CSF. Of 110 MS patients with chronic progressive disease, 107 had increased CSF anti-MBP and 2 had elevated anti-PLP. Of 87 MS patients in remission, 15 had modestly elevated anti-MBP and none had detectable anti-PLP. Considering the total of 370 clinically definite MS patients with active and inactive disease, 77% had increased CSF anti-MBP and 1% had increased CSF anti-PLP. These findings are suggesting 2 immunochemically distinct forms of MS: a common form with autoantibodies directed against MBP and a more rare form associated with anti-PLP.

Adult↗

PubMed1991

Purification of autoantibodies to myelin basic protein by antigen specific affinity chromatography from cerebrospinal fluid IgG of multiple sclerosis patients. Immunoreactivity studies with human myelin basic protein.

Immunoglobulin G (IgG) was purified by single-step protein A-Sepharose (Pharmacia) affinity chromatography from the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and controls. Autoantibodies to myelin basic protein (anti-MBP) were isolated from the purified IgG fraction by two-step antigen specific affinity chromatography. Anti-MBP in the context of whole CSF or in purified form reacts equally to MBP prepared from non-MS or MS brain tissue. Kinetic studies of anti-MBP titers demonstrate that when anti-MBP is reacted with increasing amounts of non-MS or MS MBP, the autoantibody is immunoabsorbed by either antigen in vitro. Immunoabsorption of anti-MBP by MBP or its synthetic peptides may also be possible in vivo as a potential therapeutic tool.

Autoantibodies↗

PubMed1986

Myelin basic protein inhibits histone-specific protein methylase I.

Bovine brain myelin basic protein, free of associated proteolytic activity, was found to be a specific inhibitor of histone-specific protein methylase I (S-adenosyl-L-methionine:protein-L-arginine N-methyltransferase, EC 2.1.1.23) purified from bovine brain. 50% of the methyl group incorporation into the histone substrate catalyzed by the methylase I was inhibited by myelin basic protein at a concentration of 0.326 mM. However, neither of the peptide fragments (residues 1-116 and residues 117-170) generated by the chemical cleavage of myelin basic protein at the tryptophan residue retained the inhibitory activity for histone-specific protein methylase I. Proteins such as gamma-globulin, bovine serum albumin, bovine pancreatic ribonuclease and polyarginine did not exhibit significant inhibitory activity toward the enzyme. The Ki value for myelin basic protein was estimated to be 3.42 X 10(-5) M for histone-specific protein methylase I and the nature of the inhibition was uncompetitive toward histone substrate.

Amino Acids↗

PubMed1985

Membrane proteins in reverse micelles: myelin basic protein in a membrane-mimetic environment.

The solubility, reactivity, and conformational dynamics of myelin basic protein (MBP) from bovine brain were studied in reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)-isooctane and water. Such a membrane-mimetic system resembles the aqueous spaces of native myelin sheath in terms of physicochemical properties as reflected in the high affinity of MBP for interfacial bound water. This is marked by the unusual profile of the solubility curve of the protein in reverse micelles, which shows optimal solubility at a much lower molar ratio of water to surfactant ([ H2O]/[AOT] = w0) than that reported for other water-soluble proteins. The role of counterions and/or charged polar head groups in the solubilization process is revealed by comparison of the solubility of MBP in nonionic surfactant micellar solutions. Whereas MBP is unfolded in aqueous solutions, insertion into reverse micelles generates a more folded structure, characterized by the presence of 20% alpha-helix. This conformation is unaffected by variations in the water content of the system (in the 2.0-22.4 w0 range). The reactivity of epsilon-amino groups of lysine residues with aqueous solutions of o-phthalaldehyde demonstrates that segments of the peptide chain are accessible to water. Similar results were obtained with the sequence involved in heme binding. In contrast, the sole tryptophan residue, Trp-117, is shielded from the aqueous solvent, as indicated by lack of reaction with N-bromosuccinimide. The invariance of the wavelength maximum emission in the fluorescence spectra as a function of w0 is consistent with this result.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Identification of the sites in myelin basic protein that are phosphorylated by meiosis-activated protein kinase p44mpk.

Myelin basic protein serves as a convenient substrate for detection of a 44 kDa protein-serine/threonine kinase (p44mpk) that is activated near the time of germinal vesicle breakdown in maturing echinoderm and amphibian oocytes. In vitro phosphorylation by purified p44mpk from sea star oocytes was primarily on threonine residues on a single tryptic peptide of bovine brain myelin basic protein. Amino acid composition analysis of the isolated posphopeptide revealed that it was rich in proline residues. Automated solid-phase sequencing by Edman degradation identified the major site as Thr-97 in the sequence NIVTPRTPPPSQGK, which corresponds to residues 91-104 in bovine brain myelin basic protein. Thr-94 was also phosphorylated by p44mpk to a very minor extent.

Amino Acid Sequence↗

PubMed1997

Enzyme immunoassay for myelin basic protein in cerebrospinal fluid.

Myelin basic proteins (MBPs) are a set of proteins making up about 30% of the protein content of the central nervous system myelin. Four human isoforms have been identified. The most abundant is a highly conserved 18.5 kDa polypeptide. For this species, the amino acid sequence homologies between human and monkey or human and chick are 98.2% and 71.1%, respectively. As a consequence, there is a very good immunological cross-reactivity between the mammalian MBP. This protein has been extensively used to induce experimental allergic encephalomyelits (EAE) in numerous animals. The evolution of chronic EAE in animal is similar to that of multiple sclerosis (MS), a demyelinating human pathology, and chronic EAE is considered to be an animal model of MS. In demyelinating pathologies, MBP concentration in the cerebrospinal fluid (CSF) is considered to be a good marker of demyelination. MBP concentration, in biological fluids, is generally determined by radioimmunoassay (RIA). The RIA technique currently used is highly sensitive (0.1-2.5 ng/ml) but has the drawback of requiring the handling of radioactivity and frequent labelling of MBP. So we developed a new enzyme immunoassay (EIA) technique. Our technique has the same sensitivity as RIA, needs only small volumes of CSF (50 microliters) and the enzyme-labelled MBP tracer is stable for at least 12 months.

Alkaline Phosphatase↗

PubMed1983

CSF antibodies to myelin basic protein and to myelin-associated glycoprotein in multiple sclerosis. Evidence of the intrathecal production of antibodies.

Cerebrospinal fluid (CSF) from 40 multiple sclerosis (MS) patients was tested by solid-phase radioimmunoassay (RIA) for ability to bind 2 common structural components of myelin and oligodendroglia, i.e., to bind myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). To prevent the effect of differences in CSF IgG concentration on binding activity, the CSF samples were tested at equal IgG concentration 1 mg/ml. The mean binding activity to MBP and MAG was significantly higher than in control neurotics, respectively P less than or equal to 0.05 and P less than or equal to 0.001. In 33% of MS cases, CSF antibody against both antigens was found. Indirect data were obtained that autoantibodies whose antigens are associated with myelin-oligodendrocyte unit are produced locally within the central nervous system (CNS). Anti-MAG and anti-MBP CSF antibody activity was significantly higher, P less than or equal to 0.01 for both antibody specificity, in MS cases characterized by high IgG Index, greater than or equal to 0.70 = means + SD in the neurotic group, versus MS cases characterized by normal IgG Index (less than or equal to 0.70). Correlation coefficient between antibody activity and IgG Index values was 0.785 for anti-MBP antibody, and 0.400 for anti-MAG antibody. The importance of intrathecally produced antibody to MBP and MAG lies in the fact that it indicates an active humoral autoimmune process against a myelin-oligodendrocyte unit in which more than one autoantigen is involved.

Antibodies↗

PubMed2000

Cryoelectron microscopy of protein-lipid complexes of human myelin basic protein charge isomers differing in degree of citrullination.

Myelin basic protein (MBP) is considered to be essential for the maintenance of stability of the myelin sheath. Reduction in cationicity of MBP, especially due to conversion of positively charged arginine residues to uncharged citrulline (Cit), has been found to be associated with multiple sclerosis (MS). Here, the interactions of an anionic phosphatidylserine/monosialoganglioside-G(M1) (4:1, w:w) lipid monolayer with 18.5-kDa MBP preparations from age-matched adult humans without MS (no Cit residues), with chronic MS (6 Cit), and with acute Marburg-type MS (18 Cit) were studied by transmission and ultralow dose scanning transmission electron microscopy under cryogenic conditions. Immunogold labeling and single particle electron crystallography were used to define the nature of the complexes visualized. These electron microscopical analyses showed that the three different MBP charge isomers all formed uniformly sized and regularly shaped protein-lipid complexes with G(M1), probably as hexamers, but exhibited differential association with and organization of the lipid. The least cationic Marburg MBP-Cit(18) formed the most open protein-lipid complex. The data show a disturbance in lipid-MBP interactions at the ultrastructural level that is related to degree of citrullination, and which may be involved in myelin degeneration in multiple sclerosis.

Adult↗

PubMed1999

Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis.

Oral administration of a myelin component, myelin basic protein (MBP), induces immunological unresponsiveness to CNS Ags and ameliorates murine relapsing experimental autoimmune encephalomyelitis (REAE). However, a recent clinical trial in which multiple sclerosis patients were treated with repeated doses of oral myelin was unsuccessful in reducing disease exacerbations. Therefore, we directly compared the tolerizing capacity of myelin vs MBP during REAE in B10.PL mice. Oral administration of high doses of myelin, either before disease induction or during REAE, did not provide protection from disease or decrease in vitro T cell responses. In contrast, repeated oral administration of high doses of MBP suppressed established disease and MBP-specific T cell proliferation and cytokine responses. The frequency of IL-2-, IFN-gamma-, and IL-5-secreting MBP-specific T cells declined with MBP feeding, implicating anergy and/or deletion as the mechanism(s) of oral tolerance after high Ag doses. We have previously shown that the dosage and timing of Ag administration are critical parameters in oral tolerance induction. Studies presented here demonstrate that Ag homogeneity is also important, i.e., homogeneous Ag (MBP) is more effective at inducing oral tolerance than heterogeneous Ag (myelin).

Administration, Oral↗

PubMed1989

Interaction of glycosylated human myelin basic protein with lipid bilayers.

Myelin basic protein (MBP), isolated from normal human myelin, was glycosylated with UDP-N-acetyl-D-galactosamine and a glycosyltransferase isolated from porcine submaxillary glands. MBP containing 0.85 mol of N-acetyl-D-galactosamine per mole of protein was oxidized at carbon 6 by galactose oxidase and complexed with a spin-label, Tempoamine, in order to study its interactions with lipids. When the spin-labeled MBP was reacted with lipid vesicles consisting of DSPG, DPPG, and DMPG, most of the spin-label was motionally restricted in the gel phase, with a correlation time greater than 10(-8)s. The motion increased with increasing temperature and was sensitive to the lipid phase transition. Interaction with the gel phase of DPPA caused much less motional restriction of the probe. However, melting of the lipid allowed increased interaction and motional restriction of the probe, which was only partially reversed on cooling back to the gel phase. The motional restriction of the probe in these lipids is attributed to its penetration partway into the lipid bilayer in both the gel and liquid-crystalline phases. The fact that the probe bound to the protein can penetrate partway into the bilayer suggests that other hydrophobic side chains and residues of the protein can similarly penetrate into the bilayer. Additional evidence for penetration was provided by digestion of the lipid-bound protein with endoproteinase Lys-C. When nonglycosylated and glycosylated MBP in solution was treated with Lys-C, extensive digestion occurred. A single radioactive peptide which eluted at 25 min was identified as residues 92-105.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycosylation↗

PubMed2002

Detection of myelin basic protein in cerebrospinal fluid.

Radioimmunoassay for myelin basic protein in cerebrospinal fluid is commonly used as a biochemical marker of demyelination in multiple sclerosis patients. A sensitive enzyme-linked immunosorbent assay for myelin basic protein has been recently developed, which can make a clinical evaluation of myelin basic protein in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Most multiple sclerosis patients with acute exacerbation had markedly high myelin basic protein. Longitudinal studies of multiple sclerosis patients showed that myelin basic protein in CSF increases rapidly in agreement with acute relapse and then rapidly declines and disappears. Significantly higher cerebrospinal fluid myelin basic protein levels in human T-cell lymphotropic virus Type I-associated myelopathy/tropical spastic paraparesis patients were also detected. This enzyme-linked immunosorbent assay system can be used routinely to measure myelin basic protein in cerebrospinal fluid as a useful diagnostic indicator, not only for central active demyelination as in multiple sclerosis but, also for spinal cord demyelination as in human T-cell lymphotropic virus Type I-associated myelopathy/tropical spastic paraparesis.

Adolescent↗

PubMed1997

Rearrangement and reactivation of the myelin basic protein locus in myelin-deficient (mld) mouse brain.

Myelin-deficient (mld) is a complex mutation affecting the myelin basic protein (MBP) locus of the mouse. It consists of duplication and partial inversion of the MBP gene and results in a dysfunctional MBP locus. The mutant phenotype is reversed, both in vivo and in vitro, in approximately 5% of mld oligodendrocytes. One possible mechanism for the somatic reversion is recombination between homologous sequences of the duplicated gene copies to reconstitute a functional MBP locus. There are several possible recombination events that could reconstitute a functional MBP locus by DNA rearrangement. Two of these would result in reinversion and circularization of specific MBP gene sequences, respectively. In this work polymerase chain reaction analysis was used to detect both reinverted and circularized MBP gene sequences in mld mouse tissues, indicating that DNA rearrangement at the MBP locus does occur. Analysis of individually harvested cells showed that in revertant MBP-positive mld oligodendrocytes DNA rearrangement at the MBP locus was correlated with reactivation of the MBP gene. Fluctuation analysis showed that reactivation of the MBP locus is a stochastic event occurring with a frequency of approximately 1.4 x 10(-6) per cell per cell cycle during oligodendrocyte development. The frequency of rearrangement and reactivation of the MBP locus was comparable in double mutant (mld/mld, scid/scid) and single mutant (mld/mld, +scld/+scld) mice, indicating that the scid factor is not required for MBP gene reactivation in mld. The significance of DNA rearrangement in mammalian development is discussed.

Animals↗

PubMed2000

Analogous structural motifs in myelin basic protein and in MARCKS.

Myelin basic protein (MBP) and myristoylated alanine-rich C-kinase substrate (MARCKS) are similar in terms of having extended conformations regulated by their environment (i.e., solubilised or lipid-associated), N-terminal modifications, a dual nature of interactions with lipids, binding to actin and Ca2+-calmodulin, and being substrates for different kinds of protein kinases. The further sequence similarities of segments of MBP with lipid effector regions of MARCKS, and numerous reports in the literature, support the thesis that some developmental isoform of MBP functions in signal transduction.

Amino Acid Sequence↗

PubMed1980

Phosphorylation of myelin basic protein by vaccinia virus.

Vaccinia virus phosphorylates myelin basic protein in the myelin membrane in vitro. In the presence of vaccinia virus cores maximally 1.5 mol and in the presence of intact virus 0.7 mol phosphate residues were incorporated into 1 mol of myelin basic protein in the myelin membrane. The peptides of myelin basic protein which were phosphorylated by the vaccinia virus kinase were clearly all different from the peptides which were phosphorylated by the endogenous myelin protein kinase. The viral modification of the encephalitogenic protein and its significance to immunological events is discussed.

Myelin Basic Protein↗

PubMed1997

Demyelinating antibodies to myelin oligodendrocyte glycoprotein and galactocerebroside induce degradation of myelin basic protein in isolated human myelin.

Although the specificity of multiple sclerosis (MS) brain immunoglobulins (Igs) remains unknown, the incubation of these Igs with human myelin can lead to myelin basic protein (MBP) degradation mediated by neutral proteases. In this study, we demonstrate that monoclonal antibodies (mAbs) specific to myelin components such as the CNS-specific myelin oligodendrocyte glycoprotein (MOG) and galactocerebroside (GalC) are found to induce a significant loss of MBP mediated by neutral proteases in myelin. By contrast, antibodies to periaxonal and structural components of myelin, such as MBP and myelin-associated glycoprotein, are ineffective in inducing such MBP degradation. Among the 11 different anti-MOG mAbs directed to externally located epitopes of MOG, only two were found to induce a significant degradation of MBP, suggesting that antibody-induced MBP degradation is not only antigen specific but also epitope specific. Based on the inhibition of MBP degradation in the presence of EGTA and the analysis of the degradation products obtained following incubation of myelin with mAbs to GalC and MOG (8-18C5), the neutral protease involved in this antibody-induced degradation of MBP could be calcium-activated neutral protease. Taken together, these results suggest that antibodies to GalC and MOG can play a major role in destabilizing myelin through MBP breakdown mediated by neutral proteases and thus have an important role to play in the pathogenesis of MS.

Antigens, Surface↗