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. 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.

JNK/ATF2 Pathway Is Involved in Iodinated Contrast Media-Induced Apoptosis

“…This study tested the hypothesis that contrast media can induce changes in genes that modify histone. Moreover, this study examined the differential effects of different contrast media on expression of activating transcriptional factor 2 (ATF2), a histone-modification gene that is involved in oxidative stress-induced apoptosis via JNK activation [12]. Finally, this study verified that apoptosis occurred in vivo and in vitro study after administration of contrast media.…”

“…1a). Additionally, several studies have demonstrated that ATF2 has a significant role in the process of apoptosis [12,14]. Thus, subsequent study examined the expression of ATF2 mRNA and ATF2 protein after contrast media treatment.…”

“…The JNK/ATF2 pathway has been linked with the development of apoptosis after exposure to reactive oxygen species [12]. Thus, this study examined whether the JNK pathway was activated by contrast media treatment.…”

AChE for DNA degradation

“…Therefore, a transcriptional response should exist to induce the expression of AChE isoforms after apoptotic stimuli. In this sense, AChE promoter contains AP1-like, ATF2 and Smad3/4 binding elements that allow transcriptional expression through c-jun, ATF2 and Smad3 [11,12]. The inhibition of c-jun, or its upstream activating kinase, JNK, abolishes cytotoxic-triggered transcriptional upregulation of AChE [11].…”

“…In this sense, AChE promoter contains AP1-like, ATF2 and Smad3/4 binding elements that allow transcriptional expression through c-jun, ATF2 and Smad3 [11,12]. The inhibition of c-jun, or its upstream activating kinase, JNK, abolishes cytotoxic-triggered transcriptional upregulation of AChE [11]. Therefore, a fine control of cytotoxic-mediated upregulation of AChE could be also of special interest to manipulate undesirable cellular responses in, for example, Alzheimer's disease.…”