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

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-C? (PLC?) and protein kinase C (PKC) occurred in injured spinal MNs within 72 h of injury. Moreover, some MNs positive for PLC? and PKC are also positive for avulsion-induced neuronal nitric oxide synthase (nNOS). Inhibition of PLC?/PKC signal pathway, either with PLC? inhibitor, 1-[6-((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione, or with PLC? siRNA augmented avulsion-induced MN death. 1-[6-((17 beta-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 PLC?/PKC signal pathway with PKC activator, phorbol-12-myristate-13-acetate, decreased avulsion-induced MN death. The temporal profile of PLC?/PKC signaling appears to be crucial for the survival of spinal MNs after root avulsion. Our data suggest that PLC? mediates, while PKC and nNOS are associated with, the avulsion-induced MN death in brachial plexus root avulsion.