Activation of c-jun N-terminal kinase/stress-activated protein kinase and the decreased ratio of Bcl-2 to Bax are associated with the auto-oxidized dopamine-induced apoptosis in PC12 cells.
Current concepts of the pathogenesis of Parkinson's disease center on the formation of reactive oxygen species (ROS). Dopamine is one of the major sources of ROS. In this study, the molecular events during the dopamine-induced apoptosis in PC-12 cells were studied using auto-oxidized dopamine. Auto-oxidized-dopamine induced DNA fragmentation and activation of c-jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) faster and stronger than dopamine. Furthermore, N-acetylcysteine, an antioxidant, prevented the auto-oxidized dopamine-induced JNK/SAPK activation and DNA fragmentation. Meanwhile, Bcl-2 started to decrease after onset of apoptosis, and Bax was increased up to beginning of apoptosis, and thereafter decreased. Therefore, these results suggested that activation of JNK/SAPK and the decreased ratio of antiapoptotic Bcl-2 to proapoptotic Bax appear to be associated with the dopamine-induced apoptosis.
Kang
C D
CD
Department of Biochemistry, College of Medicine, Pusan National University, South Korea. kcdshbw@hyowon.pusan.ac.kr
Jang
J H
JH
Kim
K W
KW
Lee
H J
HJ
Jeong
C S
CS
Kim
C M
CM
Kim
S H
SH
Chung
B S
BS
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010084:Oxidation-Reduction; D016716:PC12 Cells / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D016166:Free Radical Scavengers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine; D000111:Acetylcysteine