| 704327 | Nuclear retention of MBP mRNAs in the quaking viable mice. | Larocque D, etal., Neuron 2002 Dec 5;36(5):815-29. | Quaking viable (qk(v)) mice fail to properly compact myelin in their central nervous systems. Although the defect in the qk(v) mice involves a mutation affecting the expression of the alternatively spliced qk gene products, their roles in myelination are unknown. We show that the QKI RNA binding pro teins regulate the nuclear export of MBP mRNAs. Disruption of the QKI nucleocytoplasmic equilibrium in oligodendrocytes results in nuclear and perikaryal retention of the MBP mRNAs and lack of export to cytoplasmic processes, as it occurs in qk(v) mice. MBP mRNA export defect leads to a reduction in the MBP levels and their improper cellular targeting to the periphery. Our findings suggest that QKI participates in myelination by regulating the mRNA export of key protein components. | 12467586 | 2002-09-01 |
| 6483345 | Expression of MBP, PLP, MAG, CNP, and GFAP in the Human Alcoholic Brain. | Lewohl JM, etal., Alcohol Clin Exp Res. 2005 Sep;29(9):1698-705. | BACKGROUND: Chronic and excessive alcohol misuse results in neuropathological damage in the cerebral cortex. The damage includes white matter loss, brain atrophy, and selective loss of neurons in the superior frontal gyrus. Chronic alcohol misuse also results in alterations in the expression of a nu mber of genes, including a selective reprogramming of myelin gene expression in the frontal cortex. METHODS: The expression of cyclic nucleotide phosphodiesterase, glial fibrillary acidic protein, myelin-associated glycoprotein, myelin basic protein, and myelin proteolipid protein were assessed in the superior frontal gyrus and the primary motor cortex of control, uncomplicated alcoholic, and cirrhotic alcoholic cases. RESULTS: Overall, the expression of cyclic nucleotide phosphodiesterase, glial fibrillary acidic protein, myelin-associated glycoprotein, and myelin basic protein were significantly lower in the cirrhotic alcoholic cases compared with controls, with a similar tendency for myelin proteolipid protein. There was a strong correlation between the expression of the proteins studied and the brain weight of the individual case, but this interaction did not confound the overall analysis. There was no significant difference between controls and uncomplicated alcoholics. CONCLUSIONS: The loss of myelin proteins occurred without gross changes in brain pathology or brain weight and was not restricted to pathologically susceptible brain regions. It is not possible to determine whether the loss of myelin proteins in cirrhotic alcoholics is the result of cirrhosis per se or the combination of alcohol misuse and liver cirrhosis. Future studies comparing cases with alcoholic and nonalcoholic cirrhosis of the liver disease are required to elucidate this further. | 16205370 | 2005-05-01 |
| 11341455 | Myelin-reactive antibodies mediate the pathology of MBP-PLP fusion protein MP4-induced EAE. | Kuerten S, etal., Clin Immunol. 2011 Jul;140(1):54-62. doi: 10.1016/j.clim.2011.03.009. Epub 2011 Apr 13. | Experimental autoimmune encephalomyelitis (EAE) is frequently used for studies of multiple sclerosis (MS). Because in most EAE models T cells mediate the pathology in the absence of B cells/autoantibodies, the notion has evolved that also MS may be a primarily T cell-mediated disease. We have previo usly introduced MBP-PLP fusion protein (MP4)-induced EAE in C57BL/6 mice. Here we show that the disease in this model is antibody-dependent. Immunization of B cell-deficient mice did not induce EAE. When such B cell-deficient mice were, however, injected with MBP/PLP-specific antibodies in addition to the immunization with MP4, they developed disease of a severity and course that was similar to the wild-type mice. The deposition of antibodies in demyelinated lesions provided further evidence for the contribution of MBP/PLP-specific antibodies to CNS lesion formation. Based upon these data we suggest a two-stage model for the involvement of MBP/PLP-specific antibodies in autoimmune CNS pathology. | 21489887 | 2011-06-01 |
| 7349334 | Evaluation of a rat model of experimental autoimmune encephalomyelitis with human MBP as antigen. | Guo L, etal., Cell Mol Immunol. 2004 Oct;1(5):387-91. | Experimental autoimmune encephalomyelitis (EAE) is a good model for human multiple sclerosis (MS) research. However, there are some defects in the traditional models. Here, we improved the model by using the human myelin basic protein (MBP) as antigen. EAE was i nduced by immunization of female Wistar rats with human MBP. Compared with the traditional models, the new model was evaluated by clinical signs to pathological changes. The immune state of the model was assessed by the lymphocyte infiltrative response and levels of TNF-alpha, IFN-gamma, IL-10. It was found that most of rats exhibited tail tone loss and hind-limb paralysis, also there were demyelination, infiltrative lymphocyte foci, "neuronophagia" in the cortex of cerebra and the white matter of spinal cords. PBMCs and spleen lymphocytes were strongly responsive to the stimulation of MBP and PHA. The levels of TNF-alpha and IFN-gamma were altered with the severity of EAE. In the remitting phase, IL-10 was increased significantly. This study demonstrates that the animal model of EAE induced by human MBP bears resemblance to the features of human multiple sclerosis and promises to be a better model than ever before for the study of MS. | 16285900 | 2004-09-01 |
| 1358763 | Insertion of a retrotransposon in Mbp disrupts mRNA splicing and myelination in a new mutant rat. | O'Connor LT, etal., J Neurosci 1999 May 1;19(9):3404-13. | Our understanding of myelination has been greatly enhanced via the study of spontaneous mutants that harbor a defect in a gene encoding one of the major myelin proteins (myelin mutants). In this study, we describe a unique genetic defect in a new myelin mutant called the Long Evans shaker (les) rat that causes severe dysmyelination of the CNS. Myelin deficits result from disruption of the myelin basic protein (Mbp) gene caused by the insertion of an endogenous retrotransposon [early transposons (ETn) element] into a noncoding region (intron 3) of the gene. The ETn element alters the normal splicing dynamics of MBP mRNA, leading to a dramatic reduction in the levels of full-length isoforms (<5% of normal) and the appearance of improperly spliced, chimeric transcripts. Although these aberrant transcripts contain proximal coding regions of the MBP gene (exons 1-3), they are unable to encode functional proteins required to maintain the structural integrity of the myelin sheath. These chimeric transcripts seem capable, however, of producing the necessary signal to initiate and coordinate myelin gene expression because normal numbers of mature oligodendrocytes synthesizing abundant levels of other myelin proteins are present in the mutant CNS. The les rat is thus an excellent model to study alternative functions of MBP beyond its well characterized role in myelin compaction. | 10212300 | 1999-06-01 |
| 4889147 | A 1.8-Mbp fragment on chromosome 1 affects sympathetic response to stress: evaluation in reciprocal congenic strains between stroke-prone spontaneously hypertensive rat and Wistar-Kyoto rat. | Xiao B, etal., J Hypertens. 2010 Nov 8. | BACKGROUND: In the previous studies, we indicated that a gene (or genes) responsible for exaggerated sympathetic response to stress was located in a chromosome 1 QTL for blood pressure (BP) in stroke-prone spontaneously hypertensive rat (SHRSP). In this study, we narrowed down the candidate region t o a 1.8-Mbp fragment between D1Rat171 and D1Wox33, and established reciprocal congenic strains for this region. METHODS: Reciprocal congenic strains were established by introgressing the chromosomal segment from SHRSP/Izm into WKY/Izm (Wpch1.21) and vice versa (SPwch1.72). The urinary norepinephrine excretion (u-NE) was quantified with high-performance liquid chromatography in the urine collected under 6 h of cold stress (4 degrees C). ECG was recorded using the telemetry under 3 h of restraint stress, and the relative sympathetic activity was evaluated as the low frequency/high frequency ratio by the power spectral analysis. BP under the stresses was evaluated by the telemetry. RESULTS: The increases in the u-NE during the cold stress and in the low frequency/high frequency ratio under the restraint stress were significantly greater in Wpch1.21 when compared with Wistar-Kyoto (WKY) rat. The increases in BP both under the cold and the restraint stresses were significantly greater in Wpch1.21 than in WKY. In the reciprocal congenic strain, SPwch1.72, the effects of the transferred fragment on the sympathetic stress responses were confirmed as lower u-NE and low frequency/high frequency in this strain than in SHRSP. Further, the BP responses both to the cold and the restraint stresses were significantly greater in SHRSP than in SPwch1.72. CONCLUSION: These results indicated that a small fragment on chromosome 1 harbored a gene (or genes) influencing the sympathetic response to different stresses. | 21063213 | 2010-11-01 |
| 7327197 | Autoantibodies to neuron-specific proteins S100, GFAP, MBP and NGF in the serum of rats with streptozotocin-induced diabetes. | Lotosh NG, etal., Bull Exp Biol Med. 2013 May;155(1):48-51. | The appearance of autoantibodies to neuronal proteins (S100, GFAP, MBP, and NGF) in rat serum was analyzed by ELISA on days 5, 10, 17, 25, and 32 after streptozotocin injection. Simultaneously, blood glucose and insulin autoantibodies were assayed. Serum glucos e level increased on the next day after streptozotocin injection and the level of autoantibodies to insulin significantly increased on day 5 indicating the development of diabetes. The levels of antibodies to specific neuronal proteins (S100, GFAP, MBP, and NGF) also increased at this term. It is concluded that diabetes with streptozotocin is associated with damage to the blood-brain barrier. | 23667870 | 2013-09-01 |
| 12792227 | Characterization of biological pathways associated with a 1.37 Mbp genomic region protective of hypertension in Dahl S rats. | Cowley AW, etal., Physiol Genomics. 2014 Jun 1;46(11):398-410. doi: 10.1152/physiolgenomics.00179.2013. Epub 2014 Apr 8. | The goal of the present study was to narrow a region of chromosome 13 to only several genes and then apply unbiased statistical approaches to identify molecular networks and biological pathways relevant to blood-pressure salt sensitivity in Dahl salt-sensitive (SS) rats. The analysis of 13 overlappi ng subcongenic strains identified a 1.37 Mbp region on chromosome 13 that influenced the mean arterial blood pressure by at least 25 mmHg in SS rats fed a high-salt diet. DNA sequencing and analysis filled genomic gaps and provided identification of five genes in this region, Rfwd2, Fam5b, Astn1, Pappa2, and Tnr. A cross-platform normalization of transcriptome data sets obtained from our previously published Affymetrix GeneChip dataset and newly acquired RNA-seq data from renal outer medullary tissue provided 90 observations for each gene. Two Bayesian methods were used to analyze the data: 1) a linear model analysis to assess 243 biological pathways for their likelihood to discriminate blood pressure levels across experimental groups and 2) a Bayesian graphical modeling of pathways to discover genes with potential relationships to the candidate genes in this region. As none of these five genes are known to be involved in hypertension, this unbiased approach has provided useful clues to be experimentally explored. Of these five genes, Rfwd2, the gene most strongly expressed in the renal outer medulla, was notably associated with pathways that can affect blood pressure via renal transcellular Na(+) and K(+) electrochemical gradients and tubular Na(+) transport, mitochondrial TCA cycle and cell energetics, and circadian rhythms. | 24714719 | 2014-06-01 |
| 7364997 | Dahl (S x R) congenic strain analysis confirms and defines a chromosome 5 female-specific blood pressure quantitative trait locus to <7 Mbp. | Herrera VL, etal., PLoS One. 2012;7(7):e42214. doi: 10.1371/journal.pone.0042214. Epub 2012 Jul 30. | The detection of multiple sex-specific blood pressure (BP) quantitative trait loci (QTLs) in independent total genome analyses of F2 (Dahl S x R)-intercross male and female rat cohorts confirms clinical observations of sex-specific disease cause and response to treatment among hypertensive patients, and mandate the identification of sex-specific hypertension genes/mechanisms. We developed and studied two congenic strains, S.R5A and S.R5B introgressing Dahl R-chromosome 5 segments into Dahl S chromosome 5 region spanning putative BP-f1 and BP-f2 QTLs. Radiotelemetric non-stressed 24-hour BP analysis at four weeks post-high salt diet (8% NaCl) challenge, identified only S.R5B congenic rats with lower SBP (-26.5 mmHg, P = 0.002), DBP (-23.7 mmHg, P = 0.004) and MAP (-25.1 mmHg, P = 0.002) compared with Dahl S female controls at four months of age confirming BP-f1 but not BP-f2 QTL on rat chromosome 5. The S.R5B congenic segment did not affect pulse pressure and relative heart weight indicating that the gene underlying BP-f1 does not influence arterial stiffness and cardiac hypertrophy. The results of our congenic analysis narrowed BP-f1 to chromosome 5 coordinates 134.9-141.5 Mbp setting up the basis for further fine mapping of BP-f1 and eventual identification of the specific gene variant accounting for BP-f1 effect on blood pressure. | 22860086 | 1000-10-01 |
| 7394833 | Dahl (S x R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp. | Herrera VL, etal., PLoS One. 2013;8(2):e58280. doi: 10.1371/journal.pone.0058280. Epub 2013 Feb 28. | A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats. | 23469157 | 1000-11-01 |
| 11556036 | Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia. | Dionne N, etal., Glia. 2016 Jan;64(1):175-94. doi: 10.1002/glia.22923. Epub 2015 Oct 28. | In mammals, large caliber axons are ensheathed by myelin, a glial specialization supporting axon integrity and conferring accelerated and energy-efficient action potential conduction. Myelin basic protein (MBP) is required for normal myelin elaboration with ma ximal mbp transcription in oligodendrocytes requiring the upstream M3 enhancer. To further characterize the mechanism regulating mbp transcription, we defined M3 structure/function relationships by evaluating its evolutionary conservation, DNA footprints and the developmental programing conferred in mice by M3 derivatives. Multiple M3 regulatory element combinations were found to drive expression in oligodendrocytes and Schwann cells with a minimal 129 bp sequence conferring expression in oligodendrocytes throughout myelin elaboration, maintenance and repair. Unexpectedly, M3 derivatives conferred markedly different spatial and temporal expression programs thus illuminating striking transcriptional heterogeneity within post-mitotic oligodendrocytes. Finally, one M3 derivative engaged only during primary myelination, not during adult remyelination, demonstrating that transcriptional regulation in the two states is not equivalent. | 26507463 | 2016-10-01 |
| 6483446 | Immunoproteasome LMP2 60HH variant alters MBP epitope generation and reduces the risk to develop multiple sclerosis in Italian female population. | Mishto M, etal., PLoS One. 2010 Feb 18;5(2):e9287. | BACKGROUND: Albeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the production of MHC class I-restricted epitopes and t herefore its activity could be an important element in the activation and regulation of autoreactive CD8+ T cells in Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteasomes and PA28-alphabeta regulator are present in MS affected brain area and accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons, endothelial cells, oligodendrocytes, macrophages/macroglia and lymphocytes. Furthermore, in a genetic study on 1262 Italian MS cases and 845 controls we observed that HLA-A*02+ female subjects carrying the immunoproteasome LMP2 codon 60HH variant have a reduced risk to develop MS. Accordingly, immunoproteasomes carrying the LMP2 60H allele produce in vitro a lower amount of the HLA-A*0201 restricted immunodominant epitope MBP(111-119). CONCLUSION/SIGNIFICANCE: The immunoproteasome LMP2 60HH variant reduces the risk to develop MS amongst Italian HLA-A*02+ females. We propose that such an effect is mediated by the altered proteasome-dependent production of a specific MBP epitope presented on the MHC class I. Our observations thereby support the hypothesis of an involvement of immunoproteasome in the MS pathogenesis. | 20174631 | 1000-05-01 |
| 11553291 | Increased expression of NDEL1 and MBP genes in the peripheral blood of antipsychotic-naive patients with first-episode psychosis. | Ota VK, etal., Eur Neuropsychopharmacol. 2015 Dec;25(12):2416-25. doi: 10.1016/j.euroneuro.2015.09.013. Epub 2015 Oct 9. | Schizophrenia is a multifactorial neurodevelopmental disorder with high heritability. First-episode psychosis (FEP) is a critical period for determining the disease prognosis and is especially helpful for identifying potential biomarkers associated with the onset and progression of the disorder. We investigated the mRNA expression of 12 schizophrenia-related genes in the blood of antipsychotic-naive FEP patients (N=73) and healthy controls (N=73). To evaluate the influences of antipsychotic treatment and progression of the disorder, we compared the gene expression within patients before and after two months of treatment with risperidone (N=64). We observed a significantly increased myelin basic protein (MBP) and nuclear distribution protein nudE-like 1 (NDEL1) mRNA levels in FEP patients compared with controls. Comparing FEP before and after risperidone treatment, no significant differences were identified; however; a trend of relatively low NDEL1 expression was observed after risperidone treatment. Animals chronically treated with saline or risperidone exhibited no significant change in Ndel1 expression levels in the blood or the prefrontal cortex (PFC), suggesting that the trend of low NDEL1 expression observed in FEP patients after treatment is likely due to factors other than risperidone treatment (i.e., disease progression). In addition to the recognized association with schizophrenia, MBP and NDEL1 gene products also play an essential role in the functions that are deregulated in schizophrenia, such as neurodevelopment. Our data strengthen the importance of these biological processes in psychotic disorders, indicating that these changes can be detected peripherally and potentially represent putative novel blood biomarkers of susceptibility and disorder progression. | 26476704 | 2015-10-01 |
| 9685479 | Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation. | Maggipinto M, etal., J Neurosci Res. 2004 Mar 1;75(5):614-23. | Heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a trans-acting factor that mediates intracellular trafficking of myelin basic protein (MBP) mRNA to the myelin compartment in oligodendrocytes, is most abundant in the nucleus, but shuttles between the nucleus and cytoplasm. In the cytoplasm, it is associated with granules that transport mRNA from the cell body to the processes of oligodendrocytes. We found that the overall level of hnRNP A2 increased in oligodendrocytes as they differentiated into MBP-positive cells, and that this augmentation was reflected primarily in the cytoplasmic pool of hnRNP A2 present in the form of granules. The extranuclear distribution of hnRNP A2 was also observed in brain during the period of myelination in vivo. Methylation and phosphorylation have been implicated previously in the nuclear to cytoplasmic distribution of hnRNPs, so we used drugs that block methylation and phosphorylation of hnRNPs to assess their effect on hnRNP A2 distribution and mRNA trafficking. Cultures treated with adenosine dialdehyde (AdOx), an inhibitor of S-adenosyl-L-homocysteine hydrolase, or with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a drug that inhibits casein kinase 2 (CK2), maintained the preferential nuclear distribution of hnRNP A2. Treatment with either drug affected the transport of RNA trafficking granules that remained confined to the cell body. | 14991837 | 2004-01-01 |
| 7327206 | Perturbation of myelin basic protein (Mbp) splice variant expression in developing rat cerebellum following perinatal exposure to methylmercury. | Padhi BK and Pelletier G, Toxicol Lett. 2012 Sep 18;213(3):374-80. doi: 10.1016/j.toxlet.2012.07.011. Epub 2012 Jul 24. | Myelin sheaths surrounding axons are essential for saltatory conduction of nerve impulse in the central nervous system. A major protein constituent of myelin sheaths is produced by the myelin basic protein (Mbp) gene, whose expression in oligodendrocytes is con served across vertebrates. In rat, five Mbp splice variants resulting from alternative splicing of exons 2, 5 and/or 6 are characterized. We developed a PCR-based strategy to quantify individual Mbp splice variants and characterized a sixth Mbp splice variant lacking only exon 5. This newly identified splice variant is predominantly expressed in developing rat brain and has orthologs in mouse and human. Many neurotoxic chemicals can perturb myelination and Mbp gene expression. Regulation of Mbp gene expression at the post-transcriptional level was assessed following perinatal exposure to neurotoxic methylmercury (2 mg/kg b.w./day). Similar reductions in total and individual Mbp splice variant mRNA levels suggest that methylmercury-induced perturbation in Mbp gene expression occurred as a consequence of decreased oligodendrocyte cell population in absence of a significant impact on its post-transcriptional regulation. | 22835759 | 2012-09-01 |
| 7495755 | Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats. | Herrera VL, etal., PLoS One. 2013 Jul 4;8(7):e67673. doi: 10.1371/journal.pone.0067673. Print 2013. | Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP) quantitative trait loci (QTLs) that co-localized with navigational performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1x10(-5)), diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1x10(-5)), and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1x10(-5)) compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM) task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05). The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males. | 23861781 | 1000-12-01 |
| 9685293 | Shear stress alters the expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) in Schwann cells. | Gupta R, etal., J Orthop Res. 2005 Sep;23(5):1232-9. Epub 2005 Apr 25. | 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 produ ces 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. | 16140204 | 2005-12-01 |
| 11074987 | Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation. | Soragni A, etal., Mol Cell. 2015 Mar 19;57(6):1011-21. doi: 10.1016/j.molcel.2015.01.026. Epub 2015 Feb 26. | Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1 ). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly. | 25728769 | 2015-05-01 |
| 1549640 | MBP1: a novel mutant p53-specific protein partner with oncogenic properties. | Gallagher WM, etal., Oncogene 1999 Jun 17;18(24):3608-16. | Using a yeast two-hybrid screening strategy with a common tumour-derived p53 mutant as bait, we identified several mutant p53-interacting partners including the known proteins wild-type (wt) p53, hUBC9 and GBP/PIAS1. In addition, a novel protein partner was identified which we have termed MBP e='font-weight:700;'>MBP1, for Mutant p53-Binding Protein 1. MBP1 is a new member of the emerging fibulin gene family, which currently comprises fibulin-1, fibulin-2 and S1-5. Expression of MBP1 mRNA is differentially regulated both temporally during development of the mouse embryo and in a tissue-specific manner within the adult. Specific interaction between MBP1 and mutant p53 was illustrated by both two-hybrid analysis in yeast and co-immunoprecipitation in mammalian cells. MBP1 displayed the following order of binding specificity towards different p53 forms: H175 > G281 > H273 > or = W248>wt p53. Thus, MBP1 appears to bind preferentially to p53 mutants of the 'structural' rather than 'contact' class, reflecting a potential bias towards those mutants having a significant alteration in conformation from that assumed by wt p53. We propose that MBP1 is the product of a candidate oncogene as rates of both neoplastic transformation and tumour cell growth were shown to be significantly enhanced when the protein is ectopically overexpressed. Furthermore, MBP1 may play a role in determining if a 'gain of function' effect is seen with certain p53 mutants. | 10380882 | 1999-09-01 |
| 11352834 | Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-alpha and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis. | Nielsen CH, etal., PLoS One. 2016 Jan 12;11(1):e0146971. doi: 10.1371/journal.pone.0146971. eCollection 2016. | B cells are involved in driving relapsing-remitting multiple sclerosis (RRMS), as demonstrated by the positive effect of therapeutic B-cell depletion. Aside from producing antibodies, B cells are efficient antigen-presenting and cytokine-secreting cells. Diverse polyclonal stimuli have been used to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-alpha or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile for self-reactive patient B cells. In contrast, polyclonal stimulation with PMA + ionomycin and MBP revealed no difference in cytokine profile between B cells from RRMS patients and healthy donors. Expanded disability status scale (EDSS) as well as multiple sclerosis severity score (MSSS) correlated with reduced ability of B cells to produce IL-10 after stimulation with MBP, indicative of diminished B-cell immune regulatory function in patients with the most severe disease. Moreover, EDSS correlated positively with the frequencies of TNF-alpha, IL-6 and IL-10 producing B cells after polyclonal stimulation. Patient-derived, IL-10-producing B cells presented MBP85-99 poorly, as did IL-6-producing B cells, particulary in the healthy donor group. B cells from MS patients thus present antigen to T cells in a pro-inflammatory context. These findings contribute to understanding the therapeutic effects of B-cell depletion in human autoimmune diseases, including MS. | 26756931 | 1000-07-01 |
