Human Nogo-C overexpression induces HEK293 cell apoptosis via a mechanism that involves JNK-c-Jun pathway.
The neurite outgrowth inhibitor protein Nogo-A has been identified as an inhibitor of axonal regeneration, and Nogo-B as a regulator of vasculature remodeling, but the additional roles of Nogo isoforms, especially Nogo-C, have obtained little attention. Nogo-C is weakly expressed in liver and kidney compared to the high expression in skeletal muscle. Here we detected the weak expression of Nogo-C in human embryonic kidney cell line HEK293, and found that Nogo-C expressed in HEK293 could induce cell apoptosis. Further experiments demonstrated the activation of JNK/SAPK and c-Jun, but not p38 in Nogo-C expressed cells. And JNK-specific inhibitor SP600125 could reduce cell apoptosis induced by Nogo-C. Furthermore, the activation of caspase-3 and PARP, the expression and phosphorylation of p53 were also detected. The data first revealed Nogo-C expressed in HEK293 confers apoptosis by inducing caspase-3 and p53 activation through the JNK-c-Jun-dependent pathway.
Chen
Yicun
Y
The College of Life Science, Nanjing Normal University, The Jiangsu Key Laboratory of Molecular and Medical Biotechnology, Nanjing 210097, PR China.
Tang
Xiaojun
X
Cao
Xiangrong
X
Chen
Huaqun
H
Zhang
Xiran
X
D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D000070798:Nogo Proteins; D020033:Protein Isoforms / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; D016755:Proto-Oncogene Proteins c-jun; C000603199:RTN4 protein, human; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases