The JNK/AP1/ATF2 pathway is involved in H2O2-induced acetylcholinesterase expression during apoptosis.
We show that H2O2 increases acetylcholinesterase (AChE) expression via transcriptional activation through c-Jun N-terminal kinase (JNK), since the JNK inhibitor SP600125, but not the extracellular signal-regulated kinase (ERK) pathway inhibitor PD98059 or p38 kinase inhibitor SB203580, attenuated H2O2-induced AChE expression and its promoter activity. Overexpression of hemagglutinin (HA)-JNK increases H2O2-induced AChE expression and its promoter activity, whereas the dominant negative mutant form of JNK suppressed H2O2-induced AChE expression and promoter activity. Mutation analysis indicates that the major response elements for JNK in the AChE promoter are the AP1-like element (TGAGTCT) site, located within the -1565/-1569 region of the AChE promoter, and the ATF2 element (CCACGTCA), within the -2185/-2177 region. The AP1-like element binds to the transcription factors, c-jun and ATF2, while the ATF2 element binds mainly ATF2. Taken together, our results strongly suggest that H2O2 induces AChE expression via the JNK/AP1/ ATF2 signaling pathway.
Zhang
J Y
JY
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Jiang
H
H
Gao
W
W
Wu
J
J
Peng
K
K
Shi
Y F
YF
Zhang
X J
XJ
D000110:Acetylcholinesterase / Q000096:biosynthesis / Q000235:genetics*; D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation
D051698:Activating Transcription Factor 2; D018808:Transcription Factor AP-1; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D000110:Acetylcholinesterase