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The p75NTR-mediated effect of nerve growth factor in L6C5 myogenic cells.

ABSTRACT: OBJECTIVE:During muscle development or regeneration, myocytes produce nerve growth factor (NGF) as well as its tyrosine-kinase and p75-neurotrophin (p75NTR) receptors. It has been published that the p75NTR receptor could represent a key regulator of NGF-mediated myoprotective effect on satellite cells, but the precise function of NGF/p75 signaling pathway on myogenic cell proliferation, survival and differentiation remains fragmented and controversial. Here, we verified the role of NGF in the growth, survival and differentiation of p75NTR-expressing L6C5 myogenic cells, specifically inquiring for the putative involvement of the nuclear factor ?B (NF?B) and the small heat shock proteins (sHSPs) ?B-crystallin and Hsp27 in these processes. RESULTS:Although NGF was not effective in modulating myogenic cell growth or survival in both standard or stress conditions, we demonstrated for the first time that, under serum deprivation, NGF sustained the activity of some key enzymes involved in energy metabolism. Moreover, we confirmed that NGF promotes myogenic fusion and expression of the structural protein myosin heavy chain while modulating NF?B activation and the content of sHSPs correlated with the differentiation process. We conclude that p75NTR is sufficient to mediate the modulation of L6C5 myogenic differentiation by NGF in term of structural, metabolic and functional changes.

SUBMITTER: de Perini A

PROVIDER: S-EPMC5716223 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The p75<sup>NTR</sup>-mediated effect of nerve growth factor in L6C5 myogenic cells.

de Perini Alessandra A Dimauro Ivan I Duranti Guglielmo G Fantini Cristina C Mercatelli Neri N Ceci Roberta R Di Luigi Luigi L Sabatini Stefania S Caporossi Daniela D

BMC research notes 20171204 1

<h4>Objective</h4>During muscle development or regeneration, myocytes produce nerve growth factor (NGF) as well as its tyrosine-kinase and p75-neurotrophin (p75<sup>NTR</sup>) receptors. It has been published that the p75<sup>NTR</sup> receptor could represent a key regulator of NGF-mediated myoprotective effect on satellite cells, but the precise function of NGF/p75 signaling pathway on myogenic cell proliferation, survival and differentiation remains fragmented and controversial. Here, we veri ...[more]

PMID: 29202822

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Project description:Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading to a change from arginine to tryptophan at residue 100 in the mature NGF? sequence (NGFR100W) in patients with hereditary sensory and autonomic neuropathy type V (HSAN V) made it possible to distinguish the signaling mechanisms that lead to two functionally different outcomes of NGF: trophic versus nociceptive. We performed extensive biochemical, cellular, and live-imaging experiments to examine the binding and signaling properties of NGFR100W Our results show that, similar to the wild-type NGF (wtNGF), the naturally occurring NGFR100W mutant was capable of binding to and activating the TrkA receptor and its downstream signaling pathways to support neuronal survival and differentiation. However, NGFR100W failed to bind and stimulate the 75 kDa neurotrophic factor receptor (p75NTR)-mediated signaling cascades (i.e., the RhoA-Cofilin pathway). Intraplantar injection of NGFR100W into adult rats induced neither TrkA-mediated thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia based on agonism for TrkA signaling. Together, our studies provide evidence that NGFR100W retains trophic support capability through TrkA and one aspect of its nociceptive signaling, but fails to engage p75NTR signaling pathways. Our findings suggest that wtNGF acts via TrkA to regulate the delayed priming of nociceptive responses. The integration of both TrkA and p75NTR signaling thus appears to regulate neuroplastic effects of NGF in peripheral nociception.SIGNIFICANCE STATEMENT In the present study, we characterized the naturally occurring nerve growth factor NGFR100W mutant that is associated with hereditary sensory and autonomic neuropathy type V. We have demonstrated for the first time that NGFR100W retains trophic support capability through TrkA, but fails to engage p75NTR signaling pathways. Furthermore, after intraplantar injection into adult rats, NGFR100W induced neither thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia. We have also provided evidence that the integration of both TrkA- and p75NTR-mediated signaling appears to regulate neuroplastic effects of NGF in peripheral nociception. Our study with NGFR100W suggests that it is possible to uncouple trophic effect from nociceptive function, both induced by wild-type NGF.

Dataset Information

The p75NTR-mediated effect of nerve growth factor in L6C5 myogenic cells.

Publications

The p75<sup>NTR</sup>-mediated effect of nerve growth factor in L6C5 myogenic cells.

Similar Datasets

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