Role for PKC-epsilon in neuronal death induced by oxidative stress

Biochem Biophys Res Commun. 2004 Jul 30;320(3):789-94. doi: 10.1016/j.bbrc.2004.05.217.


We investigated which isoforms of PKCs can be modulated and what their roles are during l-buthionine-S,R-sulfoximine (BSO)-induced neuronal death. We observed the isoform specific translocation of PKC-epsilon from the soluble fraction to the particulate in cortical neurons treated with 10 mM BSO. The translocation of PKC-epsilon by BSO was blocked by antioxidant trolox, suggesting the PKC-epsilon as a downstream of reactive oxygen species (ROS) elevated by BSO. Trolox inhibited the ROS elevation and the neuronal death in BSO-treated cortical cells. The BSO-induced neuronal death was remarkably inhibited by both the pharmacological inhibition of PKC-epsilon with epsilonV1-2 and the functional blockade for PKC-epsilon through overexpression of PKC-epsilon V1 region, suggesting the detrimental role of PKC-epsilon. These results suggest that PKC-epsilon is the major PKC isoform involved in the pathways triggered by ROS, leading to neuronal death in BSO-treated cortical neurons.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Buthionine Sulfoximine / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Glutathione / metabolism*
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Mice
  • Neocortex / cytology
  • Neocortex / drug effects
  • Neocortex / embryology
  • Neocortex / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Oxidative Stress / physiology*
  • Peptide Fragments / pharmacology
  • Protein Kinase C-epsilon / antagonists & inhibitors
  • Protein Kinase C-epsilon / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Structure-Activity Relationship


  • Isoenzymes
  • Peptide Fragments
  • Reactive Oxygen Species
  • epsilonV1-2 peptide
  • Buthionine Sulfoximine
  • Prkce protein, mouse
  • Protein Kinase C-epsilon
  • Glutathione