Melatonin activates PKC-alpha but not PKC-epsilon in N1E-115 cells

Neurochem Int. 2001 Aug;39(2):95-102. doi: 10.1016/s0197-0186(01)00021-3.


Previous reports have revealed that calmodulin antagonism by melatonin is followed by microtubule enlargements and neurite outgrowths in neuroblastoma N1E-115 cells. In addition, activation of protein kinase C (PKC) by this neurohormone is also followed by increased vimentin phosphorylation, and reorganization of vimentin intermediate filaments (IFs) in N1E-115 cells. In this work, we further characterize the activation of PKC by melatonin in neuroblastoma N1E-115 cells. We studied the Ca(2+)-dependent effects of melatonin on PKC activity and distribution of PKC-alpha in isolated N1E-115 cell IFs. Also, the effects of melatonin on PKC-alpha translocation in comparison to PKC-epsilon, were studied in intact N1E-115 cells. The results showed that both melatonin and the PKC agonist phorbol-12-myristate-13-acetate increased PKC activity in isolated IFs. The effects of the hormone were Ca(2+)-dependent, while those caused by the phorbol ester were produced with or without Ca(2+). Also, in isolated in situ IFs, the hormone changed the distribution of PKC-alpha. In intact N1E-115 cells, melatonin elicited PKC-alpha translocation and no changes were detected in PKC-epsilon. Phorbol-12-myristate-13-acetate modified the subcellular distribution of both PKC isoforms. The results showed that melatonin selectively activates the Ca(2+)-dependent alpha isoform of PKC and suggest that PKC-alpha activation by melatonin underlies IF rearrangements and participates in neurite formation in N1E-115 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Enzyme Activation
  • Intermediate Filaments / enzymology
  • Intermediate Filaments / metabolism
  • Intermediate Filaments / ultrastructure
  • Isoenzymes / metabolism*
  • Melatonin / pharmacology*
  • Mice
  • Microscopy, Electron
  • Phorbol 12,13-Dibutyrate / metabolism
  • Protein Kinase C / metabolism*
  • Protein Kinase C-alpha
  • Protein Kinase C-epsilon
  • Protein Transport
  • Tritium
  • Tumor Cells, Cultured


  • Isoenzymes
  • Tritium
  • Phorbol 12,13-Dibutyrate
  • Prkce protein, mouse
  • Prkca protein, mouse
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Protein Kinase C-epsilon
  • Melatonin