title: para-Phenylenediamine-induced autophagy in human uroepithelial cell line mediated mutant p53 and activation of ERK signaling pathway.
abstract: para-Phenylenediamine (p-PD) is a major aromatic amine that is a widely used commercial oxidative-type hair dye. Some epidemiologic studies have suggested that the use of p-PD-based hair dyes might be related to increased risk of human malignant tumors including bladder cancer. However, the effects of p-PD on autophagy in human uroepithelial cells (SV-HUC-1) is still unclear. In this study, we demonstrate that p-PD can activate the extracellular signaling-regulated protein kinase 1/2 (ERK1/2) signaling pathway in SV-HUC-1 cells. In addition, we observed that autophagosomes increased in p-PD-treated SV-HUC-1 cells as shown by electron microscopy. Our results showed incremental increase of the concentrations, Beclin-1 and microtubule-associated protein light chain 3B (LC3B), which are important regulators of autophagosomes. In contrast, the MEK inhibitor (U0126) was suppressed autophagy and the effect of p-PD on ERK1/2, Beclin-1 and LC3B proteins expression, except for mutant p53. In this study, we demonstrated that inactivation of p53 induces a potent autophagy response. Finally, our results suggest that p-PD can activate the ERK1/2 signaling pathway and mutant p53, leading to the stimulation of autophagy in SV-HUC-1 cells. These results provide us with new insights for the understanding of the mechanism of p-PD-induced cell death in urothelial cells.
authors: Graduate Institute of Medicine, Department of Pathology, College of Medicine, Kaohsiung Medical University, and Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Ya-Chun
authors: YC
authors: Huang
authors: Wen-Chun
authors: WC
authors: Hung
authors: Soi-Moi
authors: SM
authors: Chye
authors: Wan-Tzu
authors: WT
authors: Chen
authors: Chee-Yin
authors: CY
authors: Chai
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002460:Cell Line; D004396:Coloring Agents / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006202:Hair Dyes / Q000633:toxicity; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins; D009154:Mutation; D010655:Phenylenediamines / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D019459:Urothelium / Q000166:cytology
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D004396:Coloring Agents; D006202:Hair Dyes; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010655:Phenylenediamines; D016159:Tumor Suppressor Protein p53; C029728:4-phenylenediamine