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Ca2+ involvement in activation of extracellular-signalregulated- kinase 1/2 and m-calpain after axotomy of the sciatic nerve

Mårtensson, Lisa B. LU ; Blom, Charlotta Lindwall and Dahlin, Lars B. LU (2017) In Neural Regeneration Research 12(4). p.623-628
Abstract

Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 (ERK1/2; important for proliferation) and m-calpain in vitro, and the relation to Ca2+ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis(β-aminoethyl ether)- N,N,N’,N’-tetraacetic acid (EGTA). In some experiments, 5-bromo-2′-deoxyuridine (BrdU) was added during the last 24 hours to detect proliferating cells and propidium iodide (PI) was added at the last hour to... (More)

Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 (ERK1/2; important for proliferation) and m-calpain in vitro, and the relation to Ca2+ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis(β-aminoethyl ether)- N,N,N’,N’-tetraacetic acid (EGTA). In some experiments, 5-bromo-2′-deoxyuridine (BrdU) was added during the last 24 hours to detect proliferating cells and propidium iodide (PI) was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca2+, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca2+ deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca2+ seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca2+ levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca2+ levels is likely to be a useful method to promote SC proliferation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Activation, Axotomy, Cell death, Cell proliferation, M-calpain, Nerve injury, Nerve regeneration, Neural regeneration, P-ERK1/2, Sciatic nerve, Signal transduction
in
Neural Regeneration Research
volume
12
issue
4
pages
6 pages
publisher
Shenyang Editorial Dept Neural Regeneration Res
external identifiers
  • scopus:85019082110
  • wos:000400920000026
ISSN
1673-5374
DOI
10.4103/1673-5374.205103
language
English
LU publication?
yes
id
9bdadddb-cd74-40fd-a185-dedaa1756574
date added to LUP
2017-06-02 14:18:04
date last changed
2017-09-18 11:38:46
@article{9bdadddb-cd74-40fd-a185-dedaa1756574,
  abstract     = {<p>Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 (ERK1/2; important for proliferation) and m-calpain in vitro, and the relation to Ca<sup>2+</sup> deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis(β-aminoethyl ether)- N,N,N’,N’-tetraacetic acid (EGTA). In some experiments, 5-bromo-2′-deoxyuridine (BrdU) was added during the last 24 hours to detect proliferating cells and propidium iodide (PI) was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca<sup>2+</sup>, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca<sup>2+</sup> deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca<sup>2+</sup> seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca<sup>2+</sup> levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca<sup>2+</sup> levels is likely to be a useful method to promote SC proliferation.</p>},
  author       = {Mårtensson, Lisa B. and Blom, Charlotta Lindwall and Dahlin, Lars B.},
  issn         = {1673-5374},
  keyword      = {Activation,Axotomy,Cell death,Cell proliferation,M-calpain,Nerve injury,Nerve regeneration,Neural regeneration,P-ERK1/2,Sciatic nerve,Signal transduction},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {623--628},
  publisher    = {Shenyang Editorial Dept Neural Regeneration Res},
  series       = {Neural Regeneration Research},
  title        = {Ca<sup>2+</sup> involvement in activation of extracellular-signalregulated- kinase 1/2 and m-calpain after axotomy of the sciatic nerve},
  url          = {http://dx.doi.org/10.4103/1673-5374.205103},
  volume       = {12},
  year         = {2017},
}