Activation of protein kinase C-delta attenuates kainate-induced cell death of cortical neurons.
We investigated the role of individual protein kinase C (PKC) isoforms during kainate toxicity in cortical neurons. Treatment with 50 microM kainate induced isoform-specific activation of PKC-delta according to the translocation from the soluble to the particulate fraction, while it caused remarkable decreases in PKC alpha, beta, epsilon and zeta in both fractions. Kainate-induced neuronal death was significantly increased by pharmacological inhibition of PKC-delta with rottlerin, suggesting a protective role of PKC-delta against kainate toxicity. A PKC activator phorbol 12-myristate 13-acetate remarkably attenuated the kainate-induced neuronal death. Although phorbol 12-myristate 13-acetate activates PKC-epsilon and PKC-delta, the protective effect of phorbol 12-myristate 13-acetate was almost completely abolished by rottlerin, but not by epsilonV1-2. These results suggest that activation of PKC-delta attenuates the kainate-induced cell death of cortical neurons.
Jung
Yi-Sook
YS
Department of Physiology, School of Medicine, Ajou University, Suwon, Kyungkido 442-749, Korea. yisjung@ajou.ac.kr
Lee
Bo Kyung
BK
Park
Hye-Seong
HS
Shim
Jae-Kyung
JK
Kim
Seung U
SU
Lee
Soo Hwan
SH
Baik
Eun Joo
EJ
Moon
Chang-Hyun
CH
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D018690:Excitatory Amino Acid Agonists; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate; D007608:Kainic Acid