Activity deprivation-dependent induction of the proapoptotic BH3-only protein Bim is independent of JNK/c-Jun activation during apoptosis in cerebellar granule neurons.
Bcl-2-interacting mediator of cell death (Bim), a proapoptotic BH3-only protein, plays a critical role in neuronal apoptosis. Cerebellar granule neurons (CGNs) depend on activity for their survival and undergo apoptosis when deprived of depolarizing concentration of KCl. While it has been proposed that the activation of c-Jun NH2-terminal protein kinase (JNK)/c-Jun pathway contributes to the upregulation of bim gene in neurons subjected to survival signaling withdrawal, here we show that neither inhibition of JNK activity nor expression of dominant-negative c-Jun suppresses the expression of bim gene induced by activity deprivation in CGNs. We conclude that induction of bim gene is independent of the activation of JNK/c-Jun signaling pathway by activity deprivation during apoptosis of CGNs.
Shi
Leyu
L
Department of Pharmacology, Zhongshan Medical College, SUN Yat-sen University, No. 74, Zhongshan Road 2, Guangzhou 510080, China.
Gong
Shoufang
S
Yuan
Zhongmin
Z
Ma
Chi
C
Liu
Yanling
Y
Wang
Chuanfu
C
Li
Wenming
W
Pi
Rongbiao
R
Huang
Shoujian
S
Chen
Ruzhu
R
Han
Yifan
Y
Mao
Zixu
Z
Li
Mingtao
M
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; C484585:Hrk protein, rat; D009479:Neuropeptides; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D012694:Serine; D011189:Potassium Chloride; D048031:JNK Mitogen-Activated Protein Kinases