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Author (up) Kolen, K.V.; Bruinzeel, W.; He, W.; Kimpe, N.D.; Puyvelde, L.V.; Cik, M.; Pullan, S.
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  Title Investigation of signalling cascades induced by neurotrophic Synaptolepis factor K7 reveals a critical role for novel PKCepsilon Type Journal Article
  Year 2013 Publication European Journal of Pharmacology Abbreviated Journal Eur J Pharmacol  
  Volume Issue Pages  
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  Abstract This study elucidates signalling cascades involved in the neurotrophic effects induced by an active compound of Synaptolepis kirkii, a plant that is used against snakebites and for treatment of epilepsy. The active compound of this plant, synaptolepis factor K7 (K7), is suggested to exert anti-tumoral and neurotrophic actions via modulation of PKC. In SH-SY5Y cells synthesis of the neuronal marker growth-associated protein 43 was increased upon 48h treatment with K7. Immunofluorescent staining of neurites revealed an increased neurite formation by synaptolepis factor K7. Short-term signal transduction events were followed at the level of extracellular-regulated kinase phosphorylation. Extracellular-regulated kinase (ERK) phosphorylation was transiently increased upon stimulation with synaptolepis factor K7 (300nM) with a maximal effect at 30min. Use of the general PKC inhibitor bisindolylmaleimide I blocked the K7-induced ERK phosphorylation suggesting involvement of PKC. Conversely, inhibition of conventional PKCs, alpha, beta and gamma by treatment with Go6976 did not inhibit ERK phosphorylation up to 1muM. Use of a specific-PKCepsilon translocation inhibitor peptide or RNAi-mediated knockdown of PKC-epsilon (epsilon) abolished the K7-induced ERK phosphorylation implicating PKCepsilon in K7 function. This was confirmed by the observed increase in PKCepsilon translocation and autophosphorylation induced by the compound. These data show that synaptolepis factor K7 induces neuronal differentiation of SH-SY5Y cells concomitant with a transient increase in ERK phosphorylation that is mediated by activation of PKCepsilon.  
  Address CNS Discovery Research. Electronic address: kvkolen@its.jnj.com  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0014-2999 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23340224 Approved no  
  Call Number @ @ Serial 37353  
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