Role for PKC-epsilon in neuronal death induced by oxidative stress.
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.
Jung
Yi-Sook
YS
Department of Physiology, School of Medicine, Ajou University, Suwon, Kyungkido 442-749, Republic of Korea.
Ryu
Bo Rum
BR
Lee
Bo Kyung
BK
Mook-Jung
Inhee
I
Kim
Seung Up
SU
Lee
Soo Hwan
SH
Baik
Eun Joo
EJ
Moon
Chang-Hyun
CH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C448318:epsilonV1-2 peptide; D019328:Buthionine Sulfoximine; C497256:Prkce protein, mouse; D051744:Protein Kinase C-epsilon; D005978:Glutathione