The JNK/AP1/ATF2 pathway is involved in H₂O₂-induced acetylcholinesterase expression during apoptosis

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. Over expression 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.