Protein kinase C-epsilon protects PC12 cells against methamphetamine-induced death: possible involvement of suppression of glutamate receptor

Life Sci. 2003 Feb 21;72(14):1595-607. doi: 10.1016/s0024-3205(02)02450-5.

Abstract

The involvement of PKC isoform in the methamphetamine (MA)-induced death of neuron-like PC12 cell was studied. The death and the enhanced terminal dUTP nick end labeling (TUNEL) staining were inhibited by a caspase inhibitor, z-Val-Ala-Asp- (OMe)-CH(2)F (z-VAD-fmk). However, the cell death shows neither morphological nor biochemical features of apoptosis or necrosis. The cell death was suppressed by a protein kinase C (PKC) activator, 12,13-phorbol myristate acetate, but was enhanced by PKC specific inhibitor calphostin C or bisindolylmaleimide, not by PKC inhibitor relatively specific for PKC-alpha (safingol) or PKC-delta (rottlerin). Western blotting demonstrated the expression of PKC-alpha, gamma, delta, epsilon and zeta, of which PKC-epsilon translocated from the soluble to the particulate fraction after MA-treatment. Antisense to PKC-epsilon enhanced MA-induced death. A glutamate receptor antagonist MK801 abrogated the cell death, which is reversed by PKC inhibition. These data suggest that PKC-epsilon promotes PC12 cell survival through glutamate receptor suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / toxicity*
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calpain / antagonists & inhibitors
  • Caspase Inhibitors
  • Cell Survival / physiology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • In Situ Nick-End Labeling
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / physiology*
  • Methamphetamine / toxicity*
  • Naphthalenes / pharmacology
  • Oligonucleotides, Antisense / pharmacology
  • PC12 Cells / cytology*
  • PC12 Cells / drug effects
  • PC12 Cells / enzymology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology*
  • Protein Kinase C-epsilon
  • Rats
  • Receptors, Glutamate / drug effects*
  • Receptors, Glutamate / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection

Substances

  • Adrenergic Agents
  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Naphthalenes
  • Oligonucleotides, Antisense
  • Receptors, Glutamate
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Methamphetamine
  • Prkce protein, rat
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calpain
  • calphostin C
  • Tetradecanoylphorbol Acetate
  • Calcium