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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • Cellectricon AB
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Activation, Axotomy, Cell death, Cell proliferation, M-calpain, Nerve injury, Nerve regeneration, Neural regeneration, P-ERK1/2, Sciatic nerve, Signal transduction
Original languageEnglish
Pages (from-to)623-628
Number of pages6
JournalNeural Regeneration Research
Volume12
Issue number4
Publication statusPublished - 2017 Apr 1
Publication categoryResearch
Peer-reviewedYes