Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mbp”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 145 records · Page 8Linked to original sources

Dynamics of the reactivity to MBP in multiple sclerosis.

Though many lines of evidence support the importance of myelin basic protein (MBP) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its role in multiple sclerosis (MS) is still debated as well as the significance of epitope spreading in disease progression. We characterised the response to MBP in eight MS subjects and three of these were followed over time. In one case, the follow up lasted over a 6-year period. Clonal expansion, clonal persistence and epitope spreading against other MBP determinants was detected irrespective of disease course. In one patient we identified a novel T-cell receptor variable gene (BV28S2) which may be involved in the selection of MBP determinants, as suggested by experiments performed in the presence of mismatched antigen presenting cells (APC) between two subjects compatible for HLA-DR2 subtype but differing for the epitope recognised. Our findings do not sustain a role for the response to MBP effecting on clinical course and suggest that a novel TCR gene may be involved in the recognition of unusual self antigens.

Amino Acid Sequence↗

Early onset of axonal degeneration in double (plp-/-mag-/-) and hypomyelinosis in triple (plp-/-mbp-/-mag-/-) mutant mice.

Double (plp-/-mag-/-) and triple (plp-/-mbp-/-mag-/-) null-allelic mouse lines deficient in proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) were generated and characterized genetically, biochemically, and morphologically including their behavioral capacities. The plp-/-mag-/- mutant develops a rapidly progressing axon degeneration in CNS with severe cognitive and motor coordinative deficits but has a normal longevity. CNS axons of the plp-/-mbp-/-mag-/- mouse are hypomyelinated and ensheathed by "pseudomyelin" with disturbed protein and complex lipid composition. The shiverer trait in the plp-/-mbp-/-mag-/- similar to the plp-/-mbp-/- mutant is significantly ameliorated, and its lifespan is considerably prolonged. The longevity of these dysmyelinosis mouse mutants recommends them as suitable models for the long-term evaluation of stem cell therapeutic strategies.

Animals↗

[Prevention of osteoporosis by foods and dietary supplements. Bone reinforcement factor in milk: milk basic protein (MBP)].

Milk has been drunk widely for long time, because it contains superior nutritive value. In particular, milk is the supplying source of good calcium of bioavailability, in comparison with other foods. In addition, whey protein is a by-product of cheese and casein production, and we have showed that this whey protein plays a functional role for bone remodeling (bone formation and bone resorption). And, it became clear by an examination of in vitro that there were the active substances that promote bone formation and suppress bone resorption in the basic protein fraction (milk basic protein: MBP). Furthermore, it was shown that whey protein and MBP enhanced bone strength of femur in ovariectomized rats. In addition, some human studies clearly showed that MBP improved the balance of bone metabolism and increased bone density. As for MBP, MBP, which contributes to bone health, is expected as a new food material extracted from milk.

Animals↗

[Prevention of osteoporosis by foods and dietary supplements. Milk basic protein (MBP) increases bone mineral density in young adult women and perimenopausal women].

Milk has beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein: MBP), contains components capable of promoting bone formation and inhibiting bone resorption. We tried to examine the effect of MBP on bone mineral density (BMD) and markers of bone metabolism in healthy young adult women and perimenopausal women. In the healthy young women study, we found that MBP increased BMD, by promoting bone formation and inhibiting bone resorption. In the healthy perimenopausal women study, we also found that MBP increased BMD, primarily by inhibiting bone resorption, while maintaining bone formation. Thus, bone remodeling balances become positive that leads to maintenance or increase of bone formation. MBP supplementation could be effective for bone health in a wide range of generation especially those who hate to drink milk.

Adult↗

Adaptation of TCR expression vectors for the construction of mouse-human chimeric MBP-specific TCR transgenes.

T cell receptor (TCR) transgenic mice have been used extensively to study T cell development in vivo. Such studies have demonstrated high levels of expression of the TCR transgenes. Although a number of human T cell receptors appear to play a role in the development of autoimmune diseases, in vitro studies have proven inadequate for investigation of their putative pathogenicity. Several groups have reported the isolation of myelin basic protein (MBP)-reactive T cell clones from patients with multiple sclerosis and many of the T cell receptors from such clones have been well characterized. Since a number of inbred mouse strains have demonstrated susceptibility to a similar T cell-mediated inflammatory demyelinating disease known as EAE, a useful animal model is likely to be generated by expressing human MBP-specific TCR in susceptible mice. As a first step toward this goal we have cloned a number of TCR genes into an expression vector previously used for murine TCR genes. Here we report the development of a rapid cloning system for the generation of mouse-human chimeric TCR transgene constructs and the use of this system for the production of MBP-specific TCR transgenes. Human MBP-specific TCR transgenic mice will provide a unique system for the investigation of T cell-mediated demyelinating disease in the central nervous system (CNS).

Amino Acid Sequence↗

Evidence for inhibition of MyEF-2 binding to MBP promoter by MEF-1/Pur alpha.

Myelin basic protein (MBP) is a major component of the myelin sheath whose production is developmentally controlled during myelinogenesis. Earlier studies have indicated that programmed expression of the MBP gene is regulated at the level of transcription. Evidently, the MB1 regulatory motif located between nucleotides -14 to -50 plays an important role in transcription of the MBP promoter in both in vivo systems. The MB1 element contains binding sites for the activator protein MEF-1/Pur alpha and the repressor protein MyEF-2. In this study we use bandshift assays with purified MEF-1/Pur alpha and MyEF-2 and demonstrate that binding of MyEF-2 to its target sequence is inhibited by MEF-1/Pur alpha. Under similar conditions, MyEF-2 enhances the association of MEF-1/Pur alpha with MB1 DNA. MEF-1/Pur alpha binds to MB1 in mono- and dimeric forms. Inclusion of MyEF-2 in the binding reaction increases the dimeric association of MEF-1/Pur alpha with the MB1 sequence. The use of MEF-1/Pur alpha variants in the bandshift assay suggests that two distinct regions of this protein may be involved in its binding to the MB1 sequences, and its ability to block MyEF-2 interaction with the MB1 sequence. Based on previous studies on the programmed expression of MEF-1/Pur alpha and MyEF-2 during myelination and the current findings on their interplay for binding to the MB1 motif, a model is proposed for their involvement in transcriptional regulation of the MBP gene during the course of brain development.

Adenosine Triphosphate↗

Coexpression of PMP22 gene with MBP and P0 during de novo myelination and nerve repair.

The recently cloned PMP22 gene, the rat variant of the murine growth arrest-specific gene gas3, encodes a new 22 kD integral membrane glycoprotein of peripheral myelin. By means of in situ hybridization and immunohistochemistry, we have (1) analyzed PMP22 expression in myelinated and nonmyelinated peripheral nerves, and (2) compared the spatio-temporal changes in the expression of PMP22 mRNA with the expression of the myelin genes P0 and MBP (myelin basic protein) in developing as well as degenerating and regenerating sciatic nerve of rat. (3) We further investigated the expression of PMP22 mRNA by Northern blot in cultured Schwann cells maintained under different conditions of cell growth and arrest. Expression of PMP22 mRNA is restricted to Schwann cells of myelinated peripheral nerve. Transection of sciatic nerve in adult rat leads to a simultaneous and rapid decline in both PMP22 and P0 mRNA to nondetectable levels in the degenerating distal stump. When a demyelinated and axon-free distal stump, as indicated by the lack of MBP and neurofilament immunoreactivity, was reanastomosed to its proximal counterpart, the coordinated reexpression of PMP22 and MBP succeeded axonal regeneration through the distal segment with a delay of 1-2 weeks. As in regenerating nerve, a striking synchrony of expression of PMP22 and P0 transcripts, as well as MBP immunoreactivity, could be observed during sciatic nerve development. Further, in vitro evidence suggests that, unlike NIH3T3-fibroblasts, expression of PMP22/gas3 is not strictly growth arrest-specific in Schwann cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PET imaging studies of dopamine D2 receptors: comparison of [18F]N-methylspiperone and the benzamide analogues [18F]MABN and [18F]MBP in baboon brain.

A series of positron emission tomography (PET) imaging studies was conducted in a baboon with the benzamide derivatives [18F]2,3-dimethoxy-N-[9-(4-fluorobenzyl)-9-azabicyclo[3.3.1]non an-3 beta-yl]benzamide ([18F]MABN) and [18F]2,3-dimethoxy-N-[1-(4-fluorobenzyl)piperidin-4-yl]be nza mide ([18F]MBP). Studies were also conducted with the butyrophenone [18F]N-methylspiperone (NMSP) for comparison. Tissue-time activity curves of [18F]MABN are similar to those of [18F]NMSP since both compounds displayed approximately the same uptake in the basal ganglia and displayed irreversible binding kinetics in vivo. However, the rapid rate of clearance from the cerebellum and high basal ganglia:cerebellum ratio of [18F]MABN indicate that this compound has a much lower amount of nonspecific binding than [18F]NMSP. [18F]MBP displayed a higher uptake in the basal ganglia relative to [18F]NMSP and [18F]MABN and exhibited reversible binding kinetics in vivo. This property of [18F]MBP is desirable since the uptake of radioactivity in D2-rich ligands is less likely to be influenced by changes in cerebral blood flow. The current data suggest that both [18F]MABN and [18F]MBP are promising ligands for studying dopamine D2 receptors with PET.

Animals↗

A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp.

Restriction endonuclease fragment length variations (RFLV) were detected in mice with DNA probes for myelin basic protein (Mbp), glucocorticoid receptor-1 (Grl-1), and Friend MuLV integration site-2 (Fim-2). RFLV of the Mbp gene were found in SacI restriction patterns, RFLV of the Grl-1 gene were found in EcoRV patterns, and RFLV of the Fim-2 were found in BglII patterns. A three-point backcross was carried out by the backcross mating (C57BL/KsJ-spm/spm x MOL-MIT)F1 males x C57BL/KsJ-spm/spm; spm is an autosomal recessive gene causing sphingomyelinosis. From the results, spm, Grl-1, Fim-2, and Mbp loci were mapped on chromosome 18, and the following order of genes is proposed, with distances between genes in parentheses: centromere--spm--(7.8 cM)--Grl-1--(7.8 cM)--Fim-2--(39.1 cM)--Mbp--telomere. All laboratory strains and two European subspecies (Mus mus domesticus and M. m. brevirostris) carry the Grl-1a, Fim-2a, and Mbpa alleles. In contrast, another wild subspecies from Europe (M. m. musculus) and some Asian subspecies (M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai) carry the Grl-1b, Fim-2b, and Mbpb alleles. Only castaneus strains carry the intermediate combination of the Grl-1b, Fim-2a, and Mbpb alleles.

Animals↗

Normal rate of Schwann cell proliferation in the MBP-deficient shiverer mouse during Wallerian degeneration.

Myelin basic protein (MBP) processed by macrophages was reported to promote Schwann cell division during Wallerian degeneration. In the present study we have shown that there was no difference in the rate of Schwann cell proliferation between shiverer mice, which totally lack MBP, and control mice after nerve-transection. Furthermore, addition of autologous peritoneal macrophages in cultures led to enhanced thymidine uptake by Schwann cells, irrespective of the presence or absence of MBP. These results suggest that myelin components other than MBP play a role in Schwann cell proliferation induced by macrophages.

Animals↗

Experimental allergic encephalomyelitis: clinical disease and enhanced cellular transfer in the absence of lymphocyte proliferative responses against syngeneic MBP.

Experimental allergic encephalomyelitis (EAE) was induced in Lewis rats using several different immunization protocols, and draining lymph node cells from these animals were assayed for proliferation against heterologous, homologous, and syngeneic MBP, and syngeneic spinal cord. Proliferative responses were largely stimulated by nonsyngeneic antigenic determinants and correlated better with the antigen used to induce EAE than with signs of autoimmune disease. Lymph node cells from rats immunized with either guinea pig spinal cord or syngeneic MBP did not proliferate measurably when restimulated in vitro with syngeneic MBP, yet lymphoid cells from these animals were enhanced in their capacity to transfer EAE following in vitro stimulation with syngeneic MBP.

Animals↗

Developmental profile and differential localization of mRNAs of myelin proteins (MBP and PLP) in oligodendrocytes in the brain and in culture.

We applied the in situ hybridization technique to localize the mRNAs for two myelin proteins: proteolipid protein (PLP) and myelin basic protein (MBP). In the oligodendrocyte in primary culture, PLP mRNA was located exclusively in the cell body throughout development. However, MBP mRNA was first located in the cell body and was rapidly distributed to the processes but not to the membranous sheets formed from the tips and lengths of the processes. Expression of PLP and MBP genes progressed in the caudo-cranial direction in the brain as far as we examined it in the tissue sections up to the 30th postnatal day: mRNAs of both genes were first detected in the pons and the medulla oblongata on the 3rd postnatal day and then in the cerebellum and the anterior part of the brain. PLP mRNA was located exclusively in the cell body throughout development. The number of PLP mRNA-positive cells reached a plateau in the posterior part of the brain on the 18th postnatal day, whereas it continued to increase in the anterior part of the brain by the 30th day. MBP mRNA was first expressed in the cell body, but later, it was found along the myelin sheath.

Aging↗

The development of the transferrin-transferrin receptor system in relation to astrocytes, MBP and galactocerebroside in normal and myelin-deficient rat optic nerves.

The factor(s) which control the onset of myelination are unknown. It is now accepted that transferrin (Tf), the major iron transport protein in vertebrates, is found in oligodendrocytes in the adult brain. Because of the importance of iron in basic cell metabolism we have hypothesized that iron (mobilized by Tf) may be a permissive agent in the process of myelination. The present study was designed to determine with immunohistochemistry the relationship of Tf receptor expression, Tf accumulation, and the expression of myelin components myelin basic protein (MBP) and galactocerebroside (GAlC)) in the developing rat optic nerve. In addition to Tf and its receptor, the developmental pattern for GalC reported in this study has not been examined in the rat optic nerve. Furthermore, a myelin mutant strain of rats was used to determine if a lack of myelin production affects the Tf-Tf receptor system. Our study found that Tf receptor was expressed from birth on blood vessels and was first seen in the parenchyma of the nerve at 8 days of age. The expression of the Tf receptor preceded that of Tf, MBP or GalC. The accumulation of Tf by oligodendrocytes occurred about the same time as the intracellular appearance of MBP and GalC which was shortly after the onset of myelination. Tf-positive cells as well as MBP- and GalC-positive cells increased in number and staining intensity with age whereas the expression of the Tf receptor declined after reaching a peak at 15 days of age. In the optic nerves of myelin-deficient rats, the Tf receptor expression and Tf accumulation was confined to the vasculature. The results of this study suggest that the expression of the Tf receptor is an early event in oligodendrocytic maturation and is followed by the intracellular accumulation of myelin components and Tf. The temporal association of Tf and myelin production suggests that further study is warranted regarding the possibility that the Tf-iron system supports or perhaps even permits the initiation of the process of myelination.

Aging↗

Electroimmunoblotting of myelin basic protein peptides: a novel approach to the rapid characterisation of antigenic specificities of monoclonal and polyclonal anti-MBP antibodies.

A rapid and sensitive method for the identification of antigenic determinants recognised by monoclonal and polyclonal antibodies directed against myelin basic protein (MBP) is described. By electroimmunoblotting a series of overlapping peptides covering the entire MBP molecule with monoclonal anti-MBP antibodies, the binding pattern of immunoreactive peptides can be rapidly determined and the reactive antigenic determinant identified. This procedure, which can be performed with both native and synthetic peptides, can also with appropriate modification, be applied to the analysis of naturally occurring or experimentally induced polyclonal anti-MBP autoantibodies.

Antibodies↗

Experimental allergic encephalomyelitis induced by the peptide encoded by exon 2 of the MBP gene, a peptide implicated in remyelination.

The discovery of T lymphocytes reactive to the peptide encoded by exon 2 of the myelin basic protein (MBP) gene in multiple sclerosis (MS) patients has drawn attention to MBP isoforms harboring that peptide as candidate autoantigens. Previously, immunological studies in MS had almost exclusively used the more abundant 18.5 kDa isoform of MBP, which does not contain the exon 2 peptide. Investigations of experimental allergic encephalomyelitis (EAE) have also focussed on the 18.5 kDa MBP isoform and its peptides. Since EAE is an animal model widely used to study MS, we examined the encephalitogenic potential of exon 2 peptide in the SJL/J mouse. Evidence for increased expression of exon 2-containing isoforms during remyelination in mouse CNS suggested that exon 2-sensitized T cells, with encephalitogenic capacity, might be important in the perpetuation of relapsing EAE (rEAE). Our experiments have demonstrated that exon 2 peptide is inherently immunogenic in SJL mice and that EAE could be induced by the adoptive transfer of exon 2-sensitized lymphocytes. Furthermore, the disease could be accentuated by the transfer of short-term exon 2-reactive lines or by a combination of adoptive transfer and antigenic challenge with exon 2 peptide. The immunodominant epitope(s) appeared to localize to the segment bordered by amino acids 59-85.

Amino Acid Sequence↗

Mannose binding protein (MBP) enhances mononuclear phagocyte function via a receptor that contains the 126,000 M(r) component of the C1q receptor.

Mannose-binding protein (MBP), C1q, the recognition component of the classical complement pathway, and pulmonary surfactant protein A (SP-A) are members of a family of molecules containing a collagen-like sequence contiguous with a noncollagen-like sequence, and usually having the properties of a lectin. C1q and SP-A have been shown to enhance monocyte FcR- and CR1-mediated phagocytosis, suggesting that the common structural features of the collagen-like domains may provide a basis for this immunologically important function. Results presented here demonstrate that MBP also enhanced FcR-mediated phagocytosis by both monocytes and macrophages, and stimulated CR1-mediated phagocytosis in human culture-derived macrophages and in phorbol ester-activated monocytes. Furthermore, a monoclonal antibody that recognizes a 126,000 M(r) cell surface protein and inhibits C1q-enhanced phagocytosis, inhibited the MBP-mediated enhancement of phagocytosis. Thus, the receptors that mediate the enhancement of phagocytosis by MBP and C1q share at least one critical functional component, the 126,000 M(r) ClqRP.

Carrier Proteins↗

Association of MBP peptides with Hsp70 in normal appearing human white matter.

Multiple Sclerosis is an autoimmune disease directed against myelin proteins. The etiology of MS is poorly defined though, with no definitive causative agent yet identified. It has been hypothesized that MS may be a multifactorial disease resulting in the same end product: the destruction of myelin by the immune system. In this report we describe a potential role for heat shock proteins in the pathogenesis of MS. We isolated Hsp70 from the normal appearing white matter of both MS and normal human brain and found this was actively associated with, among other things, immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro were shown to be highly immunogenic, with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. This demonstration of a specific interaction between Hsp70 and different MBP peptides, coupled with the adjuvanticity of this association is suggestive of a possible role for Hsp70 in the immunopathology associated with MS.

Adjuvants, Immunologic↗

Shear stress alters the expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) in Schwann cells.

Schwann cells within a peripheral nerve respond robustly after an axonal injury. Recent results have revealed that Schwann cells undergo concurrent proliferation and apoptosis after a chronic nerve injury that is independent of axonal pathology. Although the exact nature of the stimulus that produces this Schwann cell response remains unknown, we postulated that this response may be triggered directly by mechanical stimuli. Thus, we sought to determine how pure Schwann cells responded to a sustained shear stress in the form of laminar fluid flow by evaluating for proliferation, expression of S-100, myelin-associated glycoprotein (MAG), and myelin basic protein (MBP). Immunohistochemistry demonstrated that the Schwann cells were positive for S-100, MAG, and MBP in greater than 99% of the experimental cells. Stimulated cells also revealed an increased rate of proliferation by as much as 100% (p<.001). The mRNA expression of MAG and MBP was down-regulated by 21% (p<.035) and 18% (p<.015), respectively, in experimental cells from RT-PCR assays. Furthermore, Western blot showed a down-regulation in MAG and MBP protein expression by 29% (p<.035) and 35% (p<.02), respectively. This study provides novel information regarding Schwann cell direct response to this physical stimulus that is not secondary to an axonal injury.

Animals↗