SEARCH · PubMed Health

Results for “Myelin Basic Protein”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources

PubMed1994

Myelin basic protein peptide specificity and T-cell receptor gene usage of HPRT mutant T-cell clones in patients with multiple sclerosis.

Characterization of T cells responding to autoantigens is central to understanding autoimmune disease. We have used somatic mutation at the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene as an index of T-cell amplification in vivo. With this strategy we previously showed that myelin basic protein-reactive T cells can be isolated only from the HPRT mutant T-cell population cultured from the peripheral blood of multiple sclerosis patients and not from normal individuals. In this study, 165 HPRT mutant and 104 wild-type clones were examined for their reactivity to myelin basic protein and overlapping peptides of myelin basic protein. Five HPRT mutant clones that recognized myelin basic protein and myelin basic protein peptides along with three clones that responded to myelin basic protein peptide alone were isolated. All but one of the eight clones recognized peptides derived from the carboxy terminus of myelin basic protein (p84-168). Sequence analysis showed heterogeneous expression of T-cell receptor V alpha and V beta genes and CDR3s. These studies showed that in vivo amplified autoimmune T cells from patients with long-standing disease use diverse T-cell receptor elements in the recognition of C-terminal myelin basic protein peptides.

Adult↗

PubMed1987

Adherence of cells to myelin basic protein. II. Adherence of red blood cells of SJL mice with chronic relapsing EAE.

Adherence of red blood cells from SJL mice suffering of chronic relapsing experimental allergic encephalomyelitis was studied to myelin basic protein coated microtiter plates. Control animals received either bovine serum albumine or "protein-antigen free" adjuvant using the same immunization protocol. Characteristic changes in adherence were found in bovine or human myelin basic protein injected animals compared to the bovine serum albumine immunized group. After a nonspecific increase in adherence between Days 2 to 6 observed in all 3 groups, in the encephalitogen challenged animals on Days 13-14 a marked decrease in red blood cell adherence was detected which maintained at this decreased level during the clinically active stage of the disease and reappeared with the relapse of EAE. No such decreased adherence of red blood cells was observed in BSA immunized animals or in adherence of cells from myelin basic protein injected animals to other basic type protein such as histone. Thus, decreased adherence of red blood cells in animals with EAE appears to be an interestingly unique measure of the disease activity.

Animals↗

PubMed1990

Antigen processing of myelin basic protein is required prior to recognition by T cells inducing EAE.

The processing and presentation of whole myelin basic protein (MBP) and a 12 amino acid encephalitogenic peptide were investigated using MBP-immune and peptide-immune murine T cell lines. Myelin basic protein is the major component of central nervous system (CNS) white matter capable of inciting an autoimmune response which leads to the disease, experimental allergic encephalomyelitis (EAE), in a number of animal species. MBP-immune T cell lines caused a form of adoptively transferred EAE when injected into naive, syngeneic recipients. It has been found that both whole MBP and peptide required processing in order to induce proliferation of the T cell lines. The proliferative response was greatest when MBP was processed under conditions in which proteolysis was prevented. The demonstration that activation of encephalitogenic MBP immune T cells requires a processed form of MBP may have relevance to the human inflammatory CNS demyelinating condition, multiple sclerosis, for which EAE is the EAE is the prime animal model.

Amino Acid Sequence↗

PubMed1998

Cell-type specific factors bind to regulatory elements located downstream of the TATA-box element in the mouse myelin basic protein (MBP) gene promoter.

Cell-type specific transcription of the myelin basic protein (MBP) gene in primary oligodendrocytes (OL) is regulated by cis-acting regulatory elements located at both upstream and downstream of the TATA-box region of the MBP promoter. To identify cell-type specific factors that bind to the downstream regulatory elements, we utilised DNase I footprinting analysis and gel retardation assays with nuclear extracts from myelin-forming OL as well as a non-myelin forming cell line, C6 glioma (C6) cells. Several regions of DNA were protected from DNAse I digestion by nuclear extracts of both cell types. However, two regions, from -17 to +17 and from +47 to +58 were protected specifically in OL, while three regions, from + 17 to + 22, from +43 to +49 and from +58 to +64 were protected only with C6 nuclear extracts. Inspection of the protected regions for homology with known transcription factor binding sites revealed that sequences at from +47 to +58 and from +56 to +68 showed extensive homology to the negative regulatory element (NRE1), of the mouse renin gene and to the interferon (IFN) consensus sequence of major histocompatibility complex class I genes (MHC I-ICS), respectively. Gel retardation assays using a MHC I-ICS oligonucleotide and transient transfection assays using MBP-CAT constructs were used to study the effect of IFNs on MBP promoter activity in OL and C6 cells. In OL, IFN-alpha/beta caused little induction of CAT activity, but IFN-gamma resulted in a 2-3.5-fold decrease in CAT activity. In contrast, in C6 cells both IFN-alpha/beta and IFN-gamma induced a 1.5-2.5-fold increase in CAT activity. The cooperative effects of factors binding to NREs and ICS may be responsible for the cell-type specific regulation of MBP gene transcription.

Animals↗

PubMed1982

Binding of myelin basic protein to phospholipid micelles.

Resonances of 1H NMR spectra (360 MHz) due to several individual substituents of myelin basic protein reconstituted into phospholipid micelles have been resolved and assigned. With the aid of spin echo techniques to remove overlapping signals in the region of 2-3 ppm, singlet resonances due to the two myelin basic protein methionine S--CH3 groups (Met-20 and Met-167) and the Ala-1 N-acetyl methyl group were observed. In the presence of sufficient lysophosphatidylcholine to fully bind the protein, differential broadening occurred for Met S--CH3 resonances; Met-20 lost about 40% of its original integrated intensity (while displaying no significant line broadening) but Met-167 and N-acetyl-Ala-1 resonances did not appear to be influenced by lipid. The differential broadening of the Met-20 (versus the Met-167 and N-acetyl-Ala-1) resonances was proposed to arise from (a) specific restriction to local molecular motion of the Met-20 (but not Met-167) side chain (i.e. due to its penetration into the hydrophobic micelle lipid matrix or its proximity to specific protein/lipid electrostatic sites); or (b) transmitted dynamic effects of overall protein binding to micellar particles (due to the relatively fewer degrees of rotational freedom available to Met-20 versus N-acetyl-Ala-1 and Met-167 near protein termini). Evidence favoring the latter alternative is presented.

Animals↗

PubMed2005

Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children.

OBJECT: Misdiagnosis of inflicted traumatic brain injury (iTBI) is common. Serum biomarkers may be able to assist in the detection of iTBIs that would otherwise be missed. The authors investigated whether serum concentrations of biomarkers were increased after noninflicted (n)TBI and iTBI in pediatric cases of varying severity. METHODS: This prospective, case-control study involved 100 patients (56 with nTBI, 44 with iTBI) and 64 controls. Blood was collected in patients within 12 hours of injury; a subset had serial samples. A single sample was collected from controls. Serum neuron-specific enolase (NSE), S100B, and myelin basic protein concentrations were measured. Abnormal concentrations were defined using receiver-operator characteristic (ROC) curves. The sensitivity and specificity of initial NSE and S100B and peak myelin basic protein concentrations for identifying TBI at ROC curve-defined cutoffs were 71 and 64% (NSE), 77 and 72% (S100B), and 44 and 96% (myelin basic protein), respectively. Eighty-six percent of patients having suffered iTBI had one or more biomarkers increased, including 82% of children with iTBI and a Glasgow Coma Scale score of 15, and two children with iTBI who were initially misdiagnosed. Children with iTBI had a later peak concentration of all three biomarkers and were more likely to have increased myelin basic protein levels at admission compared with patients with nTBI. CONCLUSIONS: Serum NSE, S100B, or myelin basic protein are increased in the majority of children with acute nTBI and iTBI, including well-appearing children with iTBI in whom the diagnosis might otherwise have been missed. Differences in the time course of NSE, S100B, and myelin basic protein after nTBI and iTBI may provide insight into the pathophysiology of iTBI. These serum markers should be prospectively evaluated in a target population of infants.

Biomarkers↗

PubMed1996

Quantification of myelin basic protein in the human fetal spinal cord during the midtrimester of gestation.

The amount of myelin basic protein (MBP) was quantified in human fetal spinal cords from 12 to 24 gestational weeks (GW). MBP expression was determined by Northern blot, quantitative immunoblot, and immunocytochemistry. The development of compact myelin was analyzed by electron microscopy. Thirty-eight human fetal spinal cords were obtained after elective termination of intrauterine pregnancies from healthy women. Northern blot analysis showed a 15.8-fold increase in MBP mRNA between 12 and 18 GW. From 18 to 24 GW, MBP mRNA increased by 2.2-fold. The mRNA data paralleled immunoblot results that showed a 90.5-fold increase in MBP (0.147 ng/mg to 13.3 ng/mg tissue) between 12 and 18 GW and an approximately 11.5-fold increase between 18 and 24 GW (13.3 ng/mg to 154 ng/mg tissue). Immunocytochemical analysis also showed increased staining for MBP with advancing gestational age. At 12 GW, MBP immunoreactivity was observed in all three spinal cord funiculi. By 18 GW, MBP was expressed throughout the spinal cord white matter with the exception of the lateral corticospinal tracts and in the rostral levels of the fasciculus gracilis. With respect to myelin, at 12 GW, rare, noncompacted myelin lamellae were observed by electron microscopy. By 18 GW, discrete areas of compact myelin were observed in areas that showed MBP immunoreactivity, and at 24 GW, compact myelin was prominent throughout the white matter of the spinal cord. This study demonstrates a quantitative increase in MBP expression that is associated with myelin formation during the second trimester of human gestation. This information may provide normative data that can aid in the diagnosis of myelin disorders of the preterm, neonatal, and pediatric spinal cord.

Female↗

PubMed1990

Isolation of complementary DNAs encoding a cerebellum-enriched nuclear factor I family that activates transcription from the mouse myelin basic protein promoter.

A nuclear factor I (NFI) binding sequence in the myelin basic protein (MBP) promoter is required for brain-specific transcription. In the present study, we isolated multiple cDNAs encoding a family of NFI, NFI-B, from mouse brain cDNA libraries. These clones contain unique nucleotide sequences at their 5', 3', or middle portions, presumably as a result of alternative splicing. The entire sequence of NFI-B suggests that NFI-B is a mouse counterpart of NFI-L, which was previously isolated from rat liver. NFI-B is highly enriched in the cerebellum, in contrast with a ubiquitous NFI, CTF/NF-I. NFI-B proteins translated in vitro could bind to the MBP NFI site. Furthermore, we demonstrated by transfection experiments that NFI-B activated transcription from transfected MBP promoter in neuronal/glial NG108-15 cells.

Amino Acid Sequence↗

PubMed1983

Phosphate groups modifying myelin basic proteins are metabolically labile; methyl groups are stable.

Young and adult rats received intracranial injections of [33P]orthophosphoric acid. The time course of the appearance and decay of the radioactive label on basic proteins in isolated myelin was followed for 1 mo. Incorporation was maximal by 1 h, followed by a decay phase with a half-life of approximately 2 wk. However, radioactivity in the acid-soluble precursor pool (which always constituted at least half of the total radioactivity) decayed with a similar half-life, suggesting that the true turnover time of basic protein phosphates might be masked by continued exchange with a long-lived radioactive precursor pool. Calculations based on the rate of incorporation were made to more closely determine the true turnover time; it was found that most of the phosphate groups of basic protein turned over in a matter of minutes. Incorporation was independent of the rate of myelin synthesis but was proportional to the amount of myelin present. Experiments in which myelin was subfractionated to yield fractions differing in degree of compaction suggested that even the basic protein phosphate groups of primarily compacted myelin participated in this rapid exchange. Similar studies were carried out on the metabolism of radioactive amino acids incorporated into the peptide backbone of myelin basic proteins. The metabolism of the methyl groups of methylarginines also was monitored using [methyl-3H]methionine as a precursor. In contrast to the basic protein phosphate groups, both the peptide backbone and the modifying methyl groups had a metabolic half-life of months, which cannot be accounted for by reutilization from a pool of soluble precursor. The demonstration that the phosphate groups of myelin basic protein turn over rapidly suggests that, in contrast to the static morphological picture, basic proteins may be readily accessible to cytoplasm in vivo.

Age Factors↗

PubMed2003

Molecular dynamics exposes alpha-helices in myelin basic protein.

Molecular dynamics simulations of models of unmodified and deiminated MBP (myelin basic protein) have been performed on solvated structures with added counterions, for 10 ns using AMBER (assisted model building with energy refinement). The protein structures became extended, and a considerable number of alpha-helical segments formed spontaneously. The degree of molecular extension was greater in the deiminated species, and the alpha-helices were more transient. These structural disruptions may be operative in vivo during multiple sclerosis.

Animals↗

PubMed1990

[Isolation and purification of myelin basic protein from human brain].

A simplified procedure for isolation and purification of myelin basic protein (MBP) from human brain is described. Purified myelin from white matter was isolated at first, then delipidated with heated organic solvents. The pellet was washed with triethanolamine buffer and extracted with 0.01 mol/L HCl. Finally the protein in the acidic supernatant was purified with Sephadex G-150 column. By using three different PAGE and immunoelectrophoresis, the purified MBP was identified as a homogeneous component with an apparent molecular weight of 18.5 kd and pI 10.6. This procedure has the advantage of simplicity, rapidity, high yield and purity.

Adult↗

PubMed1989

Human T lymphocytes reactive with whole myelin recognize predominantly myelin basic protein.

Human T-cell lines and clones reactive with whole human myelin were isolated from three normal subjects by in vitro sensitization techniques. The CD4+ T-cell lines were maintained in long-term culture by periodic antigen restimulation with myelin and use of interleukin-2. Although myelin basic protein (MBP) represents only about 10% of the dry weight of myelin and the myelin-reactive T-cell populations were never exposed to purified MBP, each of the three cell lines responded to in vitro stimulation with both MBP and whole myelin. Seventeen of 18 T-cell clones derived from the myelin-reactive cell lines also responded to MBP. One myelin-reactive T-cell clone did not recognize MBP or the major myelin lipids but responded to delipidated myelin proteins suggesting that this clone recognized another myelin protein antigen. These results indicate that MBP is the predominant antigen in whole myelin recognized by human T cells under the culture conditions described. However, there is at least one additional protein antigen in myelin that is also immunogenic.

Cell Line↗

PubMed1992

Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain.

The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN'G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found in MBP; however, their relative concentrations varied significantly with the age of the animal. The amounts of MeArg and Me2(sym)Arg in MBP increased as a function of the age of the brain, whereas that of Me2(asym)Arg decreased. MBP from early-myelinating mouse brain was shown to contain a high proportion of Me2(asym)Arg, which was hardly detectable in older brain MBP. This derivative, Me2(asym)Arg, was also absent from MBP embedded in the most compact multilamellar myelin, but was present in MBP in the least compact myelin (P3B). Comparing the extent of total methylation in vivo (sum of all three arginine derivatives), MBP extracted from less-compact myelin (P3A and P3B) showed a level approx. 40% higher than that from compact myelin. MBPs isolated from dysmyelinating mutant mouse brains, such as jimpy (jp/y) and quaking (qk/qk), contained a much higher level of Me2(asym)Arg relative to the other two methyl derivatives and also in comparison with those levels in the mother brain MBP. SDS/PAGE analysis of MBPs extracted from the mutant (both jp/y and qk/qk) as well as young normal (6-13 days old) mouse brains indicated the presence of a high-molecular-mass isoform of MBP (about 32 kDa), but this isoform was not found in adult brains. These results therefore indicate that structural integrity of myelin membrane in which MBP is embedded appears to play a pivotal role in determining the extent and the kind of Me2Arg formation in MBP at the post-translational level.

Animals↗

PubMed1989

Interaction of two complementary fragments of the bovine spinal cord myelin basic protein with phospholipid bilayers. An ESR spin-label study.

The myelin basic protein (MBP) from bovine spinal cord was cleaved at the single tryptophan residue to produce an N-terminal fragment (F1) of molecular weight 12.6K and a C-terminal fragment (F2) of molecular weight 5.8K. The interactions of the two fragments with bilayers of the acidic lipid dimyristoylphosphatidylglycerol (DMPG) were compared with those of the intact protein, by using both chemical binding assays and spin-label electron spin resonance spectroscopy. The saturation binding stoichiometries of the two fragments were found to sum to that of the MBP, having values of 11, 24, and 36 mol of DMPG/mol of protein for F2, F1, and the MBP, respectively. The strength of binding was found to increase in the order F2 less than F1 less than MBP, which follows that of the net charges on the different fragments. The ionic strength dependence of the protein binding indicated that the interaction is primarily of electrostatic origin. The efficiency of displacement of the proteins by salt was in the order F2 greater than F1 greater than MBP, which correlates with both the strength of binding and the net charge on the different protein fragments. Nitroxide derivatives of phosphatidylglycerol (PG) labeled on the sn-2 chain were used to probe the protein-induced changes in the acyl chain dynamics. Both the fragments and the MBP decreased the lipid chain mobility as recorded by the C-5 atom and C-12 atom position nitroxide-PG spin-labels, in a manner which followed the protein binding curves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

A novel mutation in myelin-deficient mice results in unstable myelin basic protein gene transcripts.

Mice homozygous for the myelin-deficient (mld) mutation have an unusual phenotype in which the gene encoding myelin basic protein (MBP) is expressed at low levels and on an abnormal developmental schedule. In this report we describe the organization of the mld MBP locus, which results in this alteration of MBP expression. The mld MBP locus consists of two tandem MBP genes, with the upstream gene containing an inversion of its 3' region. We also demonstrate that although there are low steady-state levels of MBP RNA in mld mice, the mld MBP locus is transcribed at a rate comparable to that of the wild-type MBP gene, indicating that the MBP transcripts are abnormally unstable.

Animals↗

PubMed1995

Reversal of acute experimental autoimmune encephalomyelitis and prevention of relapses by treatment with a myelin basic protein peptide analogue modified to form long-lived peptide-MHC complexes.

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease induced by immunization with myelin basic protein (MBP), proteolipid protein, or encephalitogenic peptides from these myelin components. EAE resembles basic protein multiple sclerosis in some of its clinical and histologic features, and serves as an experimental model for this and other autoimmune diseases. In this study, we examine i.v. peptide therapy of EAE in detail, and show that repeated i.v. injections of MBP peptides effectively treat EAE in (PLJxSJL)F1 mice. In this study, administration of the immunodominant epitope (MBP Ac1-11) prevents MBP-induced disease, whereas the subdominant epitope MBP 31-47 is neither required nor sufficient. Intravenous administration of substituted MBP peptide analogues is also effective in treating EAE, provided the peptide side chains presumed to be involved in TCR contact and MHC binding are preserved. A substituted MBP peptide analogue that forms long-lived peptide-MHC complexes in vivo is more effective than the unmodified MBP peptide. Lower doses of the substituted peptide analogue are effective, and the effect is longer lasting than treatment with the unmodified peptide. Clinical signs of EAE are reversed by injection of the substituted peptide during the acute phase of disease. Moreover, treatment of mice in the remission phase of EAE results in a dramatically reduced incidence of relapse. In summary, we have shown that EAE can be reversed after onset and treated during remission with an MBP peptide analogue that has been modified for improved therapeutic potency.

Amino Acid Sequence↗

PubMed1994

The myelin basic protein gene is not a major susceptibility locus for multiple sclerosis in Italian patients.

To verify whether multiallelic polymorphism adjacent to the gene encoding for myelin basic protein is associated with or linked to multiple sclerosis in Italians, we studied 54 sporadic patients, 55 control subjects and 18 families with two or more affected individuals. Allelic typing was carried out by analysis of fragment length polymorphisms after DNA amplification by the polymerase chain reaction. The presence of linkage with the disease was tested according to either autosomal dominant or autosomal recessive modes of inheritance, and with or without the introduction of liability classes accounting for the age of the individuals. Furthermore sib-pair analysis was performed in 11 siblings. No evidence for association or linkage between the myelin basic protein gene polymorphism and multiple sclerosis was found. Our data indicate that in the Italian population the myelin basic protein gene does not play a major role in conferring genetic susceptibility to multiple sclerosis, and suggest that the latter is a heterogeneous phenomenon, possibly influenced by the different ethnic origin of the populations which have been investigated.

Adult↗

PubMed2001

The effects of deimination of myelin basic protein on structures formed by its interaction with phosphoinositide-containing lipid monolayers.

The recombinant 18.5-kDa charge isoform of murine myelin basic protein (rmMBP) is unmodified posttranslationally and was used to study the effects of deimination, i.e., the conversion of arginyl to citrullinyl residues, on the protein's interactions with itself and with lipids. The unmodified species rmMBP-Cit(0) (i.e., containing no citrullinyl residues) interacted with binary monolayers containing acidic (phosphatidylinositol) and nickel-chelating lipids to form paracrystalline arrays with 4.8-nm spacing. A sample of protein was deiminated to an average of 9 citrullinyl residues per molecule of protein, yielding rmMBP-Cit(9). Under both low- and high-salt conditions, this species formed better-ordered domains than rmMBP-Cit(0), viz., planar crystalline assemblies. Thus, deimination of MBP resulted in a significant alteration of its lipid-organizing and self-interaction properties that might be operative in myelin in vivo, especially in progression of the autoimmune disease multiple sclerosis. Comparisons of amino acid sequences indicated significant similarities of MBP with filaggrin, a protein that is deiminated in another autoimmune disease, rheumatoid arthritis, suggesting that comparable epitopes could be targeted in both pathologies. In contrast, binary lipid monolayers consisting of phosphatidylinositol-4-phosphate (or phosphatidylinositol-4,5-bisphosphate) and a nickel-chelating lipid formed helical tubular vesicular structures, which appeared to be induced and/or stabilized by rmMBP, especially in its deiminated form. Sequence comparisons with other actin- and phosphoinositide-binding proteins (vinculin, ActA, MARCKS) suggested that the carboxyl-terminal segment of MBP could form an amphipathic alpha helix and was the phosphoinositide binding site.

Amino Acid Sequence↗