scholarly journals The Effects of Insulin on Immortalized Rat Schwann Cells, IFRS1

2021 ◽  
Vol 22 (11) ◽  
pp. 5505
Author(s):  
Tomokazu Saiki ◽  
Nobuhisa Nakamura ◽  
Megumi Miyabe ◽  
Mizuho Ito ◽  
Tomomi Minato ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Basic Protein ◽  
Kinase Inhibitor ◽  
Mek Inhibitor ◽  
Demyelinating Diseases ◽  
Myelin Proteins ◽  
Proliferative Potential ◽  
Myelin Protein Zero ◽  
Peripheral Nerve Function ◽  
Protein Zero

Schwann cells play an important role in peripheral nerve function, and their dysfunction has been implicated in the pathogenesis of diabetic neuropathy and other demyelinating diseases. The physiological functions of insulin in Schwann cells remain unclear and therefore define the aim of this study. By using immortalized adult Fischer rat Schwann cells (IFRS1), we investigated the mechanism of the stimulating effects of insulin on the cell proliferation and expression of myelin proteins (myelin protein zero (MPZ) and myelin basic protein (MBP). The application of insulin to IFRS1 cells increased the proliferative activity and induced phosphorylation of Akt and ERK, but not P38-MAPK. The proliferative potential of insulin-stimulated IFRS1 was significantly suppressed by the addition of LY294002, a PI3 kinase inhibitor. The insulin-stimulated increase in MPZ expression was significantly suppressed by the addition of PD98059, a MEK inhibitor. Furthermore, insulin-increased MBP expression was significantly suppressed by the addition of LY294002. These findings suggest that both PI3-K/Akt and ERK/MEK pathways are involved in insulin-induced cell growth and upregulation of MPZ and MBP in IFRS1 Schwann cells.

scholarly journals Neurotrophin-4 induces myelin protein zero expression in cultured Schwann cells via the TrkB/PI3K/Akt/mTORC1 pathway

2017 ◽  
Vol 21 (2) ◽  
pp. 84-92 ◽  
Author(s):  
Wei Guo ◽  
Yan Li ◽  
Chao Sun ◽  
Hui-Quan Duan ◽  
Shen Liu ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Myelin Protein ◽  
Myelin Protein Zero ◽  
Cultured Schwann Cells ◽  
Mtorc1 Pathway ◽  
Protein Zero

scholarly journals P0 Glycoprotein Overexpression Causes Congenital Hypomyelination of Peripheral Nerves

2000 ◽  
Vol 148 (5) ◽  
pp. 1021-1034 ◽  
Author(s):  
Lawrence Wrabetz ◽  
Maria Laura Feltri ◽  
Angelo Quattrini ◽  
Daniele Imperiale ◽  
Stefano Previtali ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Peripheral Nerves ◽  
Gene Dosage ◽  
Hereditary Neuropathy ◽  
Myelin Protein Zero ◽  
Low Copy Number ◽  
Nerve Development ◽  
Protein Zero ◽  
Dose Dependent ◽  
Myelin Gene

We show that normal peripheral nerve myelination depends on strict dosage of the most abundantly expressed myelin gene, myelin protein zero (Mpz). Transgenic mice containing extra copies of Mpz manifested a dose-dependent, dysmyelinating neuropathy, ranging from transient perinatal hypomyelination to arrested myelination and impaired sorting of axons by Schwann cells. Myelination was restored by breeding the transgene into the Mpz-null background, demonstrating that dysmyelination does not result from a structural alteration or Schwann cell-extrinsic effect of the transgenic P0 glycoprotein. Mpz mRNA overexpression ranged from 30–700%, whereas an increased level of P0 protein was detected only in nerves of low copy-number animals. Breeding experiments placed the threshold for dysmyelination between 30 and 80% Mpz overexpression. These data reveal new points in nerve development at which Schwann cells are susceptible to increased gene dosage, and suggest a novel basis for hereditary neuropathy.

scholarly journals Transcriptional Regulators of the Golli/Myelin Basic Protein Locus Integrate Additive and Stealth Activities

2020 ◽  
Author(s):  
Hooman Bagheri ◽  
Hana Friedman ◽  
Kathy Siminovitch ◽  
Alan Peterson
Keyword(s):  
Nervous System ◽  
Myelin Basic Protein ◽  
Schwann Cells ◽  
Basic Protein ◽  
Cell Types ◽  
Myelin Proteins ◽  
Transcriptional Unit ◽  
Individual Autonomy ◽  
Specific Gene ◽  
Regulatory Sequences

ABSTRACTMyelin is composed of plasma membrane spirally wrapped around axons and compacted into dense sheaths by myelin associated proteins. In the central nervous system (CNS), myelin is elaborated by neuroepithelial derived oligodendrocytes and in the peripheral nervous system (PNS) by neural crest derived Schwann cells. While some myelin proteins are unique to only one lineage, myelin basic protein (Mbp) is expressed in both. Overlapping the Mbp gene is Golli, a transcriptional unit that is expressed widely both within and beyond the nervous system. A super-enhancer domain within the Golli/Mbp locus contains multiple enhancers shown previously to drive reporter construct expression specifically in oligodendrocytes or Schwann cells. In order to determine the contribution of each enhancer to the Golli/Mbp expression program and examine if interactions among these enhancers occur, we derived mouse lines in which enhancers were deleted, either singly or in different combinations, and relative mRNA accumulation was measured at key stages of development. Although super-enhancers have been shown to facilitate interaction among their component enhancers, the enhancers investigated here demonstrated functions that were largely additive. However, enhancers demonstrating autonomous activity strictly in one cell lineage, when missing, were found to significantly reduce output in the other thus revealing cryptic “stealth” activity. Further, Golli accumulation in all cell types investigated was markedly and uniformly attenuated by the absence of a key oligodendrocyte enhancer. Our observations expose a novel level of enhancer interaction and are consistent with a model in which enhancer-mediated DNA looping underlies higher-order Golli/Mbp regulatory organization.AUTHOR SUMMARYThe control of transcription is mediated through regulatory sequences that engage in a lineage and developmentally contextual manner. The Golli/Mbp locus gives rise to several mRNAs and while Mbp mRNAs accumulate exclusively in the two glial cell types that elaborate myelin, Golli mRNAs accumulate in diverse cell types both within and beyond the nervous system. To determine how the different Golli/Mbp enhancers distribute their activities and to reveal if they operate as autonomous agents or have functionally significant interactions with each other we derived multiple enhancer knock-out lines. Comparing the developmental accumulation of Mbp and Golli mRNAs revealed that the autonomous targeting capacity of multiple enhancers accurately predicted their in-situ contributions. Also, they acted in a largely additive manner indicating significant individual autonomy that can be accounted for by a simple chromatin looping model. Unexpectedly, we also uncovered cryptic “stealth” activity emanating from these same enhancers in lineages where they show no autonomous targeting capacity thus providing new insight into the control of lineage specific gene expression.

scholarly journals Proteome Profile of Myelin in the Zebrafish Brain

2021 ◽  
Vol 9 ◽  
Author(s):  
Sophie B. Siems ◽  
Olaf Jahn ◽  
Laura J. Hoodless ◽  
Ramona B. Jung ◽  
Dörte Hesse ◽  
...  
Keyword(s):  
Basic Protein ◽  
Mammalian Species ◽  
Model Organism ◽  
Protein Composition ◽  
Myelin Proteins ◽  
Myelin Protein ◽  
Immuno Electron Microscopy ◽  
Proteome Profile ◽  
Myelin Component ◽  
Protein Zero

The velocity of nerve conduction along vertebrate axons depends on their ensheathment with myelin. Myelin membranes comprise specialized proteins well characterized in mice. Much less is known about the protein composition of myelin in non-mammalian species. Here, we assess the proteome of myelin biochemically purified from the brains of adult zebrafish (Danio rerio), considering its increasing popularity as model organism for myelin biology. Combining gel-based and gel-free proteomic approaches, we identified > 1,000 proteins in purified zebrafish myelin, including all known constituents. By mass spectrometric quantification, the predominant Ig-CAM myelin protein zero (MPZ/P0), myelin basic protein (MBP), and the short-chain dehydrogenase 36K constitute 12%, 8%, and 6% of the total myelin protein, respectively. Comparison with previously established mRNA-abundance profiles shows that expression of many myelin-related transcripts coincides with the maturation of zebrafish oligodendrocytes. Zebrafish myelin comprises several proteins that are not present in mice, including 36K, CLDNK, and ZWI. However, a surprisingly large number of ortholog proteins is present in myelin of both species, indicating partial evolutionary preservation of its constituents. Yet, the relative abundance of CNS myelin proteins can differ markedly as exemplified by the complement inhibitor CD59 that constitutes 5% of the total zebrafish myelin protein but is a low-abundant myelin component in mice. Using novel transgenic reporter constructs and cryo-immuno electron microscopy, we confirm the incorporation of CD59 into myelin sheaths. These data provide the first proteome resource of zebrafish CNS myelin and demonstrate both similarities and heterogeneity of myelin composition between teleost fish and rodents.

scholarly journals How Does Protein Zero Assemble Compact Myelin?

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1832
Author(s):  
Arne Raasakka ◽  
Petri Kursula
Keyword(s):  
Basic Protein ◽  
Transmembrane Protein ◽  
Type I ◽  
Peripheral Neuropathies ◽  
Myelin Protein Zero ◽  
Open Questions ◽  
Pns Myelin ◽  
Protein Zero ◽  
Homophilic Adhesion ◽  
Electron Lucent

Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin—the lipid-rich, periodic structure of membrane pairs that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes via homophilic adhesion, forming, as revealed by electron microscopy, the electron-dense, double “intraperiod line” that is split by a narrow, electron-lucent space corresponding to the extracellular space between membrane pairs. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs myelination. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when P0 is trafficked and modified to enable myelin compaction, and how mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies.

scholarly journals How Does Protein Zero Assemble Compact Myelin?

2020 ◽  
Author(s):  
Arne Raasakka ◽  
Petri Kursula
Keyword(s):  
Basic Protein ◽  
Transmembrane Protein ◽  
Type I ◽  
Peripheral Neuropathies ◽  
Myelin Protein Zero ◽  
Open Questions ◽  
Disease Mutations ◽  
Pns Myelin ◽  
Protein Zero ◽  
Homophilic Adhesion

Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin – the lipid-rich, periodic structure that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes together via homophilic adhesion, forming a dense, macroscopic ultrastructure known as the intraperiod line. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs the formation of myelin. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when is P0 trafficked and modified to enable myelin compaction, and how disease mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies.

Thr124Met myelin protein zero mutation mimicking motor neuron disease

2021 ◽  
pp. 1-6
Author(s):  
Giulia Bisogni ◽  
Angela Romano ◽  
Amelia Conte ◽  
Giorgio Tasca ◽  
Daniela Bernardo ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Myelin Protein ◽  
Myelin Protein Zero ◽  
Protein Zero

Urokinase potentiates PDGF-induced chemotaxis of human airway smooth muscle cells

2003 ◽  
Vol 284 (6) ◽  
pp. L1020-L1026 ◽  
Author(s):  
Stephen M. Carlin ◽  
Michael Roth ◽  
Judith L. Black
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Kinase Inhibitor ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Mek Inhibitor ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Human Airway

We investigated the chemotactic action of PDGF and urokinase on human airway smooth muscle (HASM) cells in culture. Cells were put in collagen-coated transwells with 8-μm perforations, incubated for 4 h with test compounds, then fixed, stained, and counted as migrated nuclei by microscopy. Cells from all culture conditions showed some basal migration (migration in the absence of stimuli during the assay), but cells preincubated for 24 h in 10% FBS or 20 ng/ml PDGF showed higher basal migration than cells quiesced in 1% FBS. PDGFBB, PDGFAA, and PDGFABwere all chemotactic when added during the assay. PDGF chemotaxis was blocked by the phosphatidyl 3′-kinase inhibitor LY-294002, the MEK inhibitor U-0126, PGE2, formoterol, pertussis toxin, and the Rho kinase inhibitor Y-27632. Urokinase alone had no stimulatory effect on migration of quiescent cells but caused a dose-dependent potentiation of chemotaxis toward PDGF. Urokinase also potentiated the elevated basal migration of cells pretreated in 10% FBS or PDGF. This potentiating effect of urokinase appears to be novel. We conclude that PDGF and similar cytokines may be important factors in airway remodeling by redistribution of smooth muscle cells during inflammation and that urokinase may be important in potentiating the response.

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