Disease relevance of Mbp

• A deletion of MBP sequences in the genome of shiverer mice was also demonstrated. cDNAs for MBP will allow molecular investigation of the role this gene plays in both dysmyelinating and demyelinating diseases, as well as questions of MBP biosynthesis [1].
• DA and LEW rats were susceptible to experimental autoimmune encephalomyelitis (EAE) induced with MBP or MBP68-86, but the peptide was less active in DA rats than in intact MBP molecule [2].
• One week after induction of hydrocephalus, CGa1T and GPCP activity were reduced in the corpus callosum there was less MBP and PLP in the cerebrum, and myelin sheaths around axons greater than 0.4 micron in diameter were abnormally thin [3].
• Clinical expression of EAE and delayed-type hypersensitivity (DTH) responses to MBP were assessed [4].
• We assessed the developmental sequence of appearance of CNPase, MBP, MOPB, and PLP proteins in cerebellum (Cb) and corpus callosum (cc) in an experimental hypothyroidism model [5].

Psychiatry related information on Mbp

• If similar inappropriate excitations are also triggered by those immunogens specifically associated with Alzheimer's disease (beta-amyloid), AIDS dementia (gp120 and gp41), or multiple sclerosis (myelin basic protein), they might explain some of the acute, transient neurological and psychiatric symptoms associated with these disorders [6].

High impact information on Mbp

• When translated, a portion of this sequence was identical at 126 of 127 positions with the reported amino acid sequence for small MBP from the rat [1].
• Brains from mice of the homozygous shiverer genotype contained neatly reduced amounts of MBP mRNA relative to wild type [1].
• T cells specific to a central nervous system self antigen, such as myelin basic protein, can indeed induce experimental autoimmune encephalomyelitis, but such T cells may nevertheless appear in the blood of healthy individuals [7].
• We show here that autoimmune T cells specific to myelin basic protein can protect injured central nervous system neurons from secondary degeneration [7].
• A variable region gene of the T-cell receptor, V beta 8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2u mice after immunization with myelin basic protein (MBP) [8].

Chemical compound and disease context of Mbp

• Human glioma cells in which the MBP promoter was strongly active were sensitive to ganciclovir when they were transduced with MBP promoter/herpes simplex virus thymidine kinase gene-bearing retroviruses [9].
• Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain [10].
• Experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the injection of spinal cord tissue or myelin basic protein and adjuvants (Freund's or carbonyl iron or pertussis vaccine), or by adoptive immunization [11].
• A novel cyclic AMP response element, CACTTGATC, mediates forskolin induction of the myelin basic protein promoter in the rat Schwannoma line, D6P2T [12].
• Here, we investigated the efficacy of leflunomide and its mode of action in experimental autoimmune encephalomyelitis (EAE), which is a T helper cell type 1 cell-borne disease model to simulate inflammatory aspects of multiple sclerosis and was induced in Lewis rats by adoptive transfer of myelin basic protein (MBP)-specific T line cells [13].

Biological context of Mbp

• Oligonucleotides synthesized according to the established amino-acid sequence of lipophilin and the nucleotide sequence of the small myelin basic protein of the N-terminal, the central and C-terminal region of their sequences were used as hybridization probes for screening [14].
• In this way we have identified four Gtx binding sites within the first 750 bp of the MBP promoter and four Gtx binding sites within the first 1 [15].
• Immunoprecipitation of labeled DNA fragments encoding either the MBP or PLP promoter regions with this fusion protein has identified several Gtx-binding fragments, and we have confirmed these data using an electrophoretic mobility shift assay [15].
• Experiments using C7-deficient human serum to determine the role of TCC showed that selective MBP and PLP mRNA down-regulation was achieved only when C7 was reconstituted to form TCC [16].
• We performed the present neurophysiological study to define the location of nerve conduction abnormalities in EAE induced by immunization with PLP (PLP-EAE) and in EAE induced by immunization with MBP (MBP-EAE) in the Lewis rat [17].

Anatomical context of Mbp

• The expression of the lipophilin and myelin basic protein genes during development of the myelin sheath appears to be strictly coordinated [14].
• These data thus demonstrate that Gtx is expressed uniquely in differentiated oligodendrocytes in postnatal rodent brain and that its expression is regulated in parallel with the major myelin protein mRNAs, encoding MBP and PLP, under a variety of physiologically relevant circumstances [15].
• Encephalitogenic CDa+ T cell lines and clones derived from MBP-sensitized DA rats secreted IFN-gamma and TNF-alpha and proliferated to MBP and MBP89-169, but not to MBP68-88 [2].
• Conduction abnormalities are restricted to the central nervous system in experimental autoimmune encephalomyelitis induced by inoculation with proteolipid protein but not with myelin basic protein [17].
• Myelin basic protein (MBP) on the other hand is synthesized locally at the ends of cell processes where its messenger RNA is translated on free ribosomes [18].

Associations of Mbp with chemical compounds

• The TCC-mediated MBP mRNA decay was completely abrogated by HA1004, an inhibitor for the cAMP- and cGMP-dependent protein kinases, but not by H7, a protein kinase C inhibitor [16].
• Differential ultrastructural localization of myelin basic protein, myelin/oligodendroglial glycoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase in the CNS of adult rats [19].
• In contrast, at a later stage, when cells are already committed oligodendrocytes, CREB seems to play an important role as a mediator in the stimulation of myelin basic protein (MBP) expression by cyclic AMP (cAMP) [20].
• We have shown previously that addition of liposomes containing the two major glycosphingolipids of myelin, galactosylceramide (GalC) and cerebroside sulfate (CBS), to cultured oligodendrocytes (OLs) caused clustering of GalC on the extracellular surface and myelin basic protein (MBP) on the cytosolic surface to the same membrane domains [21].
• Effects of dexamethasone on the expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein genes in developing rat brain [22].

Physical interactions of Mbp

• Additionally Nkx2.2 recruited a histone deacetylase 1-mSin3A complex to the myelin basic protein promoter [23].

Enzymatic interactions of Mbp

• The activation of ERK2 was determined by immunoblotting and measurement of the activity in terms of the phosphorylating activity of immunoprecipitates with MAPK antibody on myelin basic protein [24].
• In the present study, immunoprecipitates of Trk NGF receptors from PC12 cells (+/- NGF treatment) were assayed for protein kinase activity by using the substrates myelin basic protein and histone HF1 under phosphorylating conditions optimal for protein kinase N and in the presence or absence of purine analogs [25].

Regulatory relationships of Mbp

• However, we have recently found that preimmunization with an alpha-chain TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (MBP)-specific clones did not suppress but rather augmented the severity of EAE induced by MBP-specific T cells in SJL/J mice [26].
• In this study, we have investigated whether cAMP and CREB play a role in regulating the expression of all or on the other hand particular MBP isoforms [20].
• Basic fibroblast growth factor down-regulates myelin basic protein gene expression and alters myelin compaction of mature oligodendrocytes in vitro [27].
• Autoimmune demyelination was studied in EAE induced by active challenge or by transfer of effector T-cell lines or clones specific for myelin basic protein or proteolipid apoprotein [28].
• One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes [29].

Other interactions of Mbp

• Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid protein and myelin basic protein genes in rat spinal cord injury [30].
• Stage-specific expression of myelin basic protein in oligodendrocytes involves Nkx2.2-mediated repression that is relieved by the Sp1 transcription factor [23].
• As demonstrated by in situ hybridization, MOBP gene expression occurs during development of the rat optic nerve later than that of MBP and proteolipid protein and coincides exactly with the beginning of myelin compaction [31].
• In all tracts, and at all developmental ages examined, apoptotic cells expressed the markers of mature oligodendrocytes, such as myelin basic protein, myelin-associated glycoprotein, and the Rip antigen, but not chondroitin sulfate proteoglycan, a marker of oligodendrocyte precursors [32].
• Next, we demonstrated that a single apo-transferrin intraparenchymal injection administered to P5 rat pups enabled mutant oligodendrocytes to synthesize myelin basic protein and to myelinate axons, indicating that transferrin effects mutant oligodendrocyte maturation regardless of its source [33].

Analytical, diagnostic and therapeutic context of Mbp

• Cellular localization of MBP mRNA by in situ hybridization further revealed that transcripts were concentrated within oligodendrocyte cell bodies instead of uniformly distributed throughout processes [34].
• Northern blot analysis indicated that diminishing protein levels could not be attributed to changes in transcriptional activity, except for MBP of which mRNA levels decreased with age [34].
• Ultrastructural immunocytochemistry allowed quantitative analysis of antigen density in different myelin and oligodendrocyte zones: MBP was detectable in high density over the whole myelin sheath, but not in regions of loops, somata, or the oligodendrocyte plasma membrane [19].
• In vitro translation followed by myelin basic protein-specific immunoprecipitation showed a direct stimulatory effect of T3 on myelin basic protein mRNA translation [35].
• Passive EAE was readily induced by adoptive transfer of MBP-specific T cell lines to syngeneic recipients [36].

References