Antiapoptotic role of NF-kappaB in the auto-oxidized dopamine-induced apoptosis of PC12 cells.
Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species (ROS), and dopamine has been considered to be a major source of ROS. Recently, it has been shown in a postmortem study that nuclear translocation of nuclear factor-kappa B (NF-kappaB) was observed in dopaminergic neurons of patient with PD. However, its role is not known. The present study examined the possible role of NF-kappaB in ODA (auto-oxidized dopamine)-induced apoptosis to understand the process of PD. Using the electrophoretic mobility shift assay, it was found that ODA activated the DNA binding activity of NF-kappaB. Suppression of the transcriptional activity of NF-kappaB in PC12 cells by overexpression of a wild-type and a dominant negative mutant form (S32A/S36A) of inhibitor kappa B (IkappaB)-alpha led to increase of apoptotic cell death induced by treatment of ODA. In addition, overexpression of NF-kappaB in PC12 cells blocked ODA-induced cell death. However, JNK/SAPK activities, which mediate various stress signals, were similar among the parental, NF-kappaB- or dominant negative mutant IkappaB alpha-transfected cells. Therefore, these results suggest that activation of NF-kappaB during ODA-induced apoptosis may have a counteracting activity against the signals mediating apoptotic cell death and thereby delay the process of Parkinson's disease.
Lee
H J
HJ
Department of Biochemistry, College of Medicine, Pusan National University, Korea.
Kim
S H
SH
Kim
K W
KW
Um
J H
JH
Lee
H W
HW
Chung
B S
BS
Kang
C D
CD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D005799:Genes, Dominant; D020672:I-kappa B Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism*; D051381:Rats; D051996:Transcription Factor RelA; D014162:Transfection
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C104705:dopamine quinone; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine