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Activation of MAPK pathways and downstream transcription factors in 2‐aminobiphenyl‐induced apoptosis

Chen, Lei‐Chin, Chueh, Tsung‐Cheng, Tuan, Yen‐Fan, Chen, Chien‐Cheng, Chien, Chih‐Ching, Lee, Huey‐Yin, Chen, Ssu‐Ching
Environmental toxicology 2015 v.30 no.2 pp. 205-211
DNA damage, acetylcysteine, apoptosis, caspase-3, mitogen-activated protein kinase, oxidative stress, signal transduction, transcription factors
2‐Aminobiphenyls (2‐ABP) induces oxidative DNA damage and leads to apoptosis. The precise signaling pathways of inducing apoptosis in vitro are still unknown. This study provides insight into the relationship between 2‐ABP‐induced apoptosis and the activation of MAPK and downstream transcription factors using pharmacological inhibitors of ERK, p38, and JNK pathways. Results showed that 2‐ABP induced the activation of ERK and JNK but not p38. The ERK/JNK pathways downstream transcription factors, c‐Jun and ATF‐2, were also activated by 2‐ABP. The inhibitory effects of ERK inhibitor, U0126, on 2‐ABP‐induced caspase‐3 activity were not detected. However, JNK inhibitor, SP600125, significantly attenuated the caspase‐3 activity induced by 2‐ABP. The expression of the transcription factors c‐Jun and ATF‐2 were decreased in 2‐ABP treated cells in the presence of ERK/JNK inhibitors, suggesting that the expression of ERK/JNK pathways leads to the downstream activation of c‐Jun and ATF‐2. N‐acetylcysteine, an ROS scavenger, inhibited 2‐ABP‐induced activation of ERK and JNK, the cell death and caspase‐3 activity, which suggested that oxidative stress plays a crucial role in apoptosis through activation of caspase‐3 in a ROS/JNK‐dependent signaling cascade. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 205–211, 2015.