scholarly journals Identification of multiple in vivo phosphorylation sites in rabbit myelin basic protein.

1983 ◽  
Vol 258 (2) ◽  
pp. 930-937 ◽  
Author(s):  
R E Martenson ◽  
M J Law ◽  
G E Deibler
Keyword(s):  
Myelin Basic Protein ◽  
Basic Protein ◽  
Phosphorylation Sites

scholarly journals Myelin basic protein enhances axonal regeneration from neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng
Keyword(s):  
Myelin Basic Protein ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Axonal Regeneration ◽  
Neural Progenitor Cells ◽  
Basic Protein ◽  
Neural Progenitor ◽  
Dependent Manner ◽  
Cord Injury

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

scholarly journals Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury

2012 ◽  
Vol 116 (1) ◽  
pp. 246-253 ◽  
Author(s):  
Robert E. Ayer ◽  
Nazanin Jafarian ◽  
Wanqiu Chen ◽  
Richard L. Applegate ◽  
Austin R. T. Colohan ◽  
...  
Keyword(s):  
Brain Injury ◽  
Myelin Basic Protein ◽  
Cerebral Edema ◽  
Transforming Growth Factor ◽  
Basic Protein ◽  
Immunological Tolerance ◽  
Neurological Injury ◽  
Mucosal Tolerance ◽  
Surgical Brain Injury

Object Intracranial surgery causes cortical injury from incisions, hemorrhage, retraction, and electrocautery. The term “surgical brain injury” (SBI) has been developed to categorize this injury inherent to the procedure. Neuroinflammation plays a significant role in SBI. Traditional antiinflammatory therapies are often limited by their immunosuppressive side effects and poor CNS penetration. This study uses mucosal tolerance to develop an immune system that is tolerant to brain myelin basic protein (MBP) so that inflammation can be suppressed in a timely and site-specific manner following surgical disruption of the blood-brain barrier. Methods A standard SBI model using CD57 mice was used. Nasopharyngeal mucosa was exposed to vehicle, ovalbumin, or MBP to develop mucosal tolerance to these antigens. Immunological tolerance to MBP was confirmed in vivo through hypersensitivity testing. Neurological scores, cerebral edema, and interleukin (IL)–1β and transforming growth factor (TGF)–β1 cytokine levels were measured 48 hours postoperatively. Results Hypersensitivity testing confirmed the development of immune tolerance to MBP. Myelin basic protein–tolerant mice demonstrated reduced neurological injury, less cerebral edema, decreased levels of IL-1β, and increased levels of TGFβ1 following SBI. Conclusions Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.

In vitro and in vivo phosphorylation of myelin basic protein by cerebral protein kinase

Nature ◽  
1974 ◽  
Vol 249 (5453) ◽  
pp. 150-151 ◽  
Author(s):  
EISHICHI MIYAMOTO ◽  
SHIRO KAKIUCHI ◽  
YASUO KAKIMOTO
Keyword(s):  
Protein Kinase ◽  
Myelin Basic Protein ◽  
Basic Protein

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

1992 ◽  
Vol 287 (3) ◽  
pp. 929-935 ◽  
Author(s):  
N Rawal ◽  
Y J Lee ◽  
W K Paik ◽  
S Kim
Keyword(s):  
Myelin Basic Protein ◽  
Mouse Brain ◽  
Structural Integrity ◽  
Basic Protein ◽  
Mutant Mouse ◽  
Highly Sensitive ◽  
Sds Page ◽  
Formation Method ◽  
Methyl Derivatives

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.

scholarly journals Signs of Myelin Impairment in Cerebrospinal Fluid After Osmotic Opening of the Blood-Brain Barrier in Rats

2015 ◽  
pp. S603-S608 ◽  
Author(s):  
P. KOZLER ◽  
O. SOBEK ◽  
J. POKORNÝ
Keyword(s):  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Blood Brain Barrier ◽  
Basic Protein ◽  
Brain Barrier ◽  
In Vivo Experiment ◽  
Blood Brain ◽  
Significant Difference ◽  
The Brain

A number of clinical neurological pathologies are associated with increased permeability of the blood brain barrier (BBB). Induced changes of the homeostatic mechanisms in the brain microenvironment lead among others to cellular changes in the CNS. The question was whether some of these changes can be induced by osmotic opening of BBB in an in vivo experiment and whether they can be detected in cerebrospinal fluid (CSF). CSF was taken via the suboccipital puncture from 10 healthy rats and six rats after the osmotic opening of the BBB. In all 16 animals, concentration of myelin basic protein (MBP ng/ml), Neuron-specific enolase (NSE ng/ml) and Tau-protein (Tau pg/ml) were determined in CSF by ELISA. Values in both groups were statistically evaluated. Significant difference between the control and experimental group was revealed only for the concentration of myelin basic protein (p<0.01). The presented results indicate that osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions of the brain leads to a damage of myelin, without impairment of neurons or their axons.

Loss of p27Kip1 function results in increased proliferative capacity of oligodendrocyte progenitors but unaltered timing of differentiation

Development ◽  
1999 ◽  
Vol 126 (18) ◽  
pp. 4027-4037 ◽  
Author(s):  
P. Casaccia-Bonnefil ◽  
R.J. Hardy ◽  
K.K. Teng ◽  
J.M. Levine ◽  
A. Koff ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Growth Arrest ◽  
Proliferating Cells ◽  
Differentiation Markers ◽  
Oligodendrocyte Progenitors ◽  
Cell Divisions ◽  
Glial Progenitors

In many tissues, progenitor cells permanently withdraw from the cell cycle prior to commitment towards a differentiated phenotype. In the oligodendrocyte lineage a counting mechanism has been proposed, linking the number of cell divisions to growth arrest and differentiation. A direct prediction of this model is that an increase in the number of cell divisions would result in a delayed onset of differentiation. Since the cell cycle inhibitor p27Kip1 is an essential component of the machinery leading to oligodendrocyte progenitor growth arrest, we examined the temporal relationship between cell cycle withdrawal and expression of late differentiation markers in vivo, in mice carrying a targeted deletion in the p27Kip1 gene. Using bromodeoxyuridine to label proliferating cells, quaking (QKI) to identify embryonic glial progenitors, NG2 to identify neonatal oligodendrocyte progenitors, and myelin basic protein to label differentiated oligodendrocytes, we found an increased number of proliferating QKI- and NG2-positive cells in germinal zones of p27Kip1(−/−) mice at the peak of gliogenesis. However, no delay was observed in these mice in the appearance of the late differentiation marker myelin basic protein in the developing corpus callosum and cerebellum. Significantly, a decrease in cyclin E levels was observed in the brain of p27Kip1 null mice coincident with oligodendrocyte growth arrest. We conclude that two distinct modalities of growth arrest occur in the oligodendrocyte lineage: a p27Kip1-dependent mechanism of growth arrest affecting proliferation in early phases of gliogenesis, and a p27Kip1-independent event leading to withdrawal from the cell cycle and differentiation.

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