Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells

Stevens, Beth; Ishibashi, Tomoko; Chen, Jiang‐Fan; Fields, R. Douglas

doi:10.1017/s1740925x04000055

Cited by 61 publications

(64 citation statements)

References 49 publications

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“…These results reveal transcripts of several genes not previously reported as being expressed in Schwann cells, such as the A2 A purinergic receptor. As we report elsewhere, further analysis confirms that the A2 A receptor is expressed in Schwann cells; where it signals through the mitogen-acitvated protein kinase (MAPK) pathway to regulate Schwann cell proliferation in culture (Stevens et al, 2004). In addition, transcripts for several other categories of genes mediating functions not typically associated with Schwann cells are found by this analysis, indicating intriguing areas for further research.…”

Section: Nhscssupporting

confidence: 82%

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

et al. 2004

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AbstractcDNA microarrays were utilized to identify abnormally expressed genes in a malignant peripheral nerve sheath tumor (MPNST)-derived cell line, T265, by comparing the mRNA abundance profiles with that of normal human Schwann cells (nhSCs). The findings characterize the molecular phenotype of this important cell-line model of MPNSTs, and elucidate the contribution of Schwann cells in MPNSTs. In total, 4608 cDNA sequences were screened and hybridizations replicated on custom cDNA microarrays. In order to verify the microarray data, a large selection of differentially expressed mRNA transcripts were subjected to semi-quantitative reverse transcription PCR (LightCycler). Western blotting was performed to investigate a selection of genes and signal transduction pathways, as a further validation of the microarray data. The data generated from multiple microarray screens, semi-quantitative RT-PCR and Western blotting are in broad agreement. This study represents a comprehensive gene-expression analysis of an MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs in culture. This study has identified ~900 genes that are expressed abnormally in the T265 cell line and detected many genes not previously reported to be expressed in nhSCs. The results provide crucial information on the T265 cells that is essential for investigation using this cell line in experimental studies in neurofibromatosis type I (NF1), and important information on normal human Schwann cells that is applicable to a wide range of studies on Schwann cells in cell culture.

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Section: Nhscssupporting

confidence: 82%

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

et al. 2004

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“…The effect of ATP on proliferation in the co-culture system is induced by the action of P 2 Y 1 receptors. However, Schwann cells also express A2 A adenosine receptors, which elevate intracellular cAMP levels and activate the ERK1/2 pathway (Stevens et al, 2004). Like ATP, adenosine inhibits Schwann cell proliferation acting via A2 A receptors but does not inhibit 04 expression or myelination.…”

Section: Purinergic Signalingmentioning

confidence: 99%

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

Jessen

Mirsky

2008

Glia

451

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Dedifferentiation of myelinating Schwann cells is a key feature of nerve injury and demyelinating neuropathies. We review recent evidence that this dedifferentiation depends on activation of specific intracellular signaling molecules that drive the dedifferentiation program. In particular, we discuss the idea that Schwann cells contain negative transcriptional regulators of myelination that functionally complement positive regulators such as Krox-20, and that myelination is therefore determined by a balance between two opposing transcriptional programs. Negative transcriptional regulators should be expressed prior to myelination, downregulated as myelination starts but reactivated as Schwann cells dedifferentiate following injury. The clearest evidence for a factor that works in this way relates to c-Jun, while other factors may include Notch, Sox-2, Pax-3, Id2, Krox-24, and Egr-3. The role of cell-cell signals such as neuregulin-1 and cytoplasmic signaling pathways such as the extracellular-related kinase (ERK)1/2 pathway in promoting dedifferentiation of myelinating cells is also discussed. We also review evidence that neurotrophin 3 (NT3), purinergic signaling, and nitric oxide synthase are involved in suppressing myelination. The realization that myelination is subject to negative as well as positive controls contributes significantly to the understanding of Schwann cell plasticity. Negative regulators are likely to have a major role during injury, because they promote the transformation of damaged nerves to an environment that fosters neuronal survival and axonal regrowth. In neuropathies, however, activation of these pathways is likely to be harmful because they may be key contributors to demyelination, a situation which would open new routes for clinical intervention. V V C 2008 Wiley-Liss, Inc.

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“…Given that P2 receptors have been reported to signal to MAPK [20,21], we next determined whether UTP-induced Ncadherin expression in SCs is mediated by the MAPK pathway. We treated RT4-D6P2T cells with UTP at different times and concentrations and analysed the lysates by Western blotting for three phosphorylated MAPKs: mitogenic MAPK ERK1/2, and the two stress-related MAPKs JNK and p38.…”

Section: Phosphorylation Of Mapk Mediates N-cadherin Expressionmentioning

confidence: 99%

N-cadherin expression is regulated by UTP in schwannoma cells

Martiáñez

Lamarca

Casals

et al. 2012

Purinergic Signalling

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Schwann cells (SCs) are peripheral myelinating glial cells that express the neuronal Ca 2+ -dependent cell adhesion molecule, neural cadherin (N-cadherin). Ncadherin is involved in glia-glia and axon-glia interactions and participates in many key events, which range from the control of axonal growth and guidance to synapse formation and plasticity. Extracellular UTP activates P2Y purinergic receptors and exerts short-and long-term effects on several tissues to promote wound healing. Nevertheless, the contribution of P2Y receptors in peripheral nervous system functions is not completely understood. The current study demonstrated that UTP induced a dose-and timedependent increase in N-cadherin expression in SCs. Furthermore, N-cadherin expression was blocked by the P2 purinoceptor antagonist suramin. The increased N-cadherin expression induced by UTP was mediated by phosphorylation of mitogen-activated protein kinases (MAPKs), such as Jun N-terminal kinase, extracellular-regulated kinase and p38 kinase. Moreover, the Rho kinase inhibitor Y27632, the phospholipase C inhibitor U73122 and the protein kinase C inhibitor calphostin C attenuated the UTP-induced activation of MAPKs significantly. Extracellular UTP also modulated increased in the expression of the early transcription factors c-Fos and c-Jun. We also demonstrated that the region of the N-cadherin promoter between nucleotide positions −3698 and −2620, which contained one activator protein-1-binding site, was necessary for UTP-induced gene expression. These results suggest a novel role for P2Y purinergic receptors in the regulation of N-cadherin expression in SCs.

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Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells

Cited by 61 publications

References 49 publications

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

N-cadherin expression is regulated by UTP in schwannoma cells

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