Activation of phospholipase-Cγ and protein kinase C signal pathways helps the survival of spinal motoneurons injured by root avulsion

J Neurochem. 2012 May;121(3):362-72. doi: 10.1111/j.1471-4159.2012.07696.x. Epub 2012 Mar 14.

Abstract

The signaling transduction processes involved in avulsion-induced motoneuron (MN) death have not been elucidated. Using the brachial plexus root avulsion rat model, we showed that avulsion-activated phosphorylation of phospholipase-Cγ (PLCγ) and protein kinase C (PKC) occurred in injured spinal MNs within 72 h of injury. Moreover, some MNs positive for PLCγ and PKC are also positive for avulsion-induced neuronal nitric oxide synthase (nNOS). Inhibition of PLCγ/PKC signal pathway, either with PLCγ inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione, or with PLCγ siRNA augmented avulsion-induced MN death. 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione also inhibited PKC phosphorylation and exacerbated avulsion-induced reductions in the nNOS protein level in injured spinal segments. Moreover, activation of PLCγ/PKC signal pathway with PKC activator, phorbol-12-myristate-13-acetate, decreased avulsion-induced MN death. The temporal profile of PLCγ/PKC signaling appears to be crucial for the survival of spinal MNs after root avulsion. Our data suggest that PLCγ mediates, while PKC and nNOS are associated with, the avulsion-induced MN death in brachial plexus root avulsion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Count
  • Cell Death / drug effects
  • Estrenes / pharmacology
  • Fluorescent Antibody Technique
  • Injections, Spinal
  • Male
  • Motor Neurons / drug effects*
  • Motor Neurons / pathology*
  • NADPH Dehydrogenase / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Phosphodiesterase Inhibitors / pharmacology
  • Phospholipase C gamma / physiology*
  • Phosphorylation
  • Protein Kinase C / physiology*
  • Pyrrolidinones / pharmacology
  • RNA, Small Interfering / pharmacology
  • Radiculopathy / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Spinal Cord / pathology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Estrenes
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • RNA, Small Interfering
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Nitric Oxide Synthase Type I
  • NADPH Dehydrogenase
  • Protein Kinase C
  • Phospholipase C gamma
  • Tetradecanoylphorbol Acetate