PMID- 18514417 OWN - NLM STAT- MEDLINE DCOM- 20081014 LR - 20161124 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 439 IP - 2 DP - 2008 Jul 11 TI - Protein kinase C-mediated protection of motoneurons from excitotoxicity. PG - 143-6 LID - 10.1016/j.neulet.2008.05.004 [doi] AB - Amyotrophic lateral sclerosis (ALS) is a progressive motoneuron disease, whose pathogenesis remains unclear. Phorbol 12-myristate 13-acetate (PMA) has been shown to be neurotrophic and neuroprotective in several types of neurons in culture. However, the survival effect of PMA on motoneurons has not been reported. Therefore, we investigated this using purified rat motoneurons. PMA showed a small but significant neurotrophic activity, which was inhibited by GF109203X, a protein kinase C (PKC) inhibitor. Under the conditions in which the survival of motoneurons is supported by brain-derived neurotrophic factor (BDNF), excitotoxicity was induced by glutamate. PMA markedly protected motoneurons against excitotoxicity. The up-regulation of PKC in the spinal cord of ALS patients was previously reported, therefore, the present results indicate that PKC activation might be involved in neuroprotection. FAU - Tomimatsu, Naoko AU - Tomimatsu N AD - Clinical Research Center, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. FAU - Arakawa, Yoshihiro AU - Arakawa Y LA - eng PT - Journal Article DEP - 20080508 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Enzyme Inhibitors) RN - 0 (Excitatory Amino Acids) RN - 0 (Indoles) RN - 0 (Maleimides) RN - 0 (Neuroprotective Agents) RN - 3KX376GY7L (Glutamic Acid) RN - 57716-89-9 (4-O-methyl-12-O-tetradecanoylphorbol 13-acetate) RN - EC 2.7.11.13 (Protein Kinase C) RN - L79H6N0V6C (bisindolylmaleimide I) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Embryo, Mammalian MH - Enzyme Inhibitors/pharmacology MH - Excitatory Amino Acids/*toxicity MH - Glutamic Acid/*toxicity MH - Indoles/pharmacology MH - Maleimides/pharmacology MH - Motor Neurons/*drug effects MH - Neuroprotective Agents/pharmacology MH - Protein Kinase C/*metabolism MH - Rats MH - Spinal Cord/cytology MH - Tetradecanoylphorbol Acetate/analogs & derivatives/pharmacology EDAT- 2008/06/03 09:00 MHDA- 2008/10/15 09:00 CRDT- 2008/06/03 09:00 PHST- 2008/03/27 00:00 [received] PHST- 2008/04/29 00:00 [revised] PHST- 2008/05/03 00:00 [accepted] PHST- 2008/06/03 09:00 [pubmed] PHST- 2008/10/15 09:00 [medline] PHST- 2008/06/03 09:00 [entrez] AID - S0304-3940(08)00620-4 [pii] AID - 10.1016/j.neulet.2008.05.004 [doi] PST - ppublish SO - Neurosci Lett. 2008 Jul 11;439(2):143-6. doi: 10.1016/j.neulet.2008.05.004. Epub 2008 May 8.