title: Activation of MAPK pathways and downstream transcription factors in 2-aminobiphenyl-induced apoptosis.
abstract: 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.
authors.affiliation: Department of Nutrition, I-Shou University, Kaohsiung City, 84001, Taiwan.
authors.forename: Lei-Chin
authors.initials: LC
authors.lastname: Chen
authors.forename: Tsung-Cheng
authors.initials: TC
authors.lastname: Chueh
authors.forename: Yen-Fan
authors.initials: YF
authors.lastname: Tuan
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Chien
authors.forename: Huey-Yin
authors.initials: HY
authors.lastname: Lee
authors.forename: Ssu-Ching
authors.initials: SC
authors.lastname: Chen
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D051698:Activating Transcription Factor 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D000611:Aminobiphenyl Compounds; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C014970:2-aminodiphenyl; D053148:Caspase 3; D000111:Acetylcysteine
keywords: 2-aminobiphenyl; ATF-2; ERK; JNK; N-acetylcysteine; c-Jun; caspase-3