Abstract
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.