Protein kinase C-epsilon protects PC12 cells against methamphetamine-induced death: possible involvement of suppression of glutamate receptor.
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.
Uemura
Koichi
K
Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo, 113-0033, Tokyo, Japan. kuemura@m.u-tokyo.jp
Aki
Toshihiko
T
Yamaguchi
Kazuhito
K
Yoshida
Ken ichi
Ki
D018663:Adrenergic Agents / Q000633:toxicity*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002154:Calpain / Q000037:antagonists & inhibitors; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008694:Methamphetamine / Q000633:toxicity*; D009281:Naphthalenes / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D018663:Adrenergic Agents; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009281:Naphthalenes; D016376:Oligonucleotides, Antisense; D017470:Receptors, Glutamate; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D008694:Methamphetamine; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002154:Calpain; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium