title: Activation of phospholipase-Cγ and protein kinase C signal pathways helps the survival of spinal motoneurons injured by root avulsion.
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.
authors.affiliation: Zhong Shan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiu-Chun
authors.initials: XC
authors.lastname: Zhao
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
authors.forename: Ya-Qiong
authors.initials: YQ
authors.lastname: Wang
authors.forename: Fa-Huan
authors.initials: FH
authors.lastname: Song
authors.forename: Ying-Qin
authors.initials: YQ
authors.lastname: Li
authors.forename: Rao
authors.initials: R
authors.lastname: Fu
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zheng
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007278:Injections, Spinal; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D011760:Pyrrolidinones / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011843:Radiculopathy / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D034741:RNA, Small Interfering; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase; D011493:Protein Kinase C; D051966:Phospholipase C gamma; D013755:Tetradecanoylphorbol Acetate