Document Detail

Protein kinase C-mediated protection of motoneurons from excitotoxicity.
MedLine Citation:
PMID:  18514417     Owner:  NLM     Status:  MEDLINE    
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.
Naoko Tomimatsu; Yoshihiro Arakawa
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Publication Detail:
Type:  Journal Article     Date:  2008-05-08
Journal Detail:
Title:  Neuroscience letters     Volume:  439     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-10     Completed Date:  2008-10-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  143-6     Citation Subset:  IM    
Clinical Research Center, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
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MeSH Terms
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Interactions
Embryo, Mammalian
Enzyme Inhibitors / pharmacology
Excitatory Amino Acids / toxicity*
Glutamic Acid / toxicity*
Indoles / pharmacology
Maleimides / pharmacology
Motor Neurons / drug effects*
Neuroprotective Agents / pharmacology
Protein Kinase C / metabolism*
Spinal Cord / cytology
Tetradecanoylphorbol Acetate / analogs & derivatives,  pharmacology
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Excitatory Amino Acids; 0/Indoles; 0/Maleimides; 0/Neuroprotective Agents; 133052-90-1/bisindolylmaleimide I; 16561-29-8/Tetradecanoylphorbol Acetate; 56-86-0/Glutamic Acid; 57716-89-9/4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; EC Kinase C

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