Graduate Institute of Medicine, Department of Pathology, College of Medicine, Kaohsiung Medical University, and Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Toxicol In Vitro. 2011 Dec;25(8):1630-7. doi: 10.1016/j.tiv.2011.06.013. Epub 2011 Jun 30.
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.
对苯二胺（p-PD）是一种广泛用于商业氧化型染发剂的主要芳香胺。一些流行病学研究表明，使用基于 p-PD 的染发剂可能与人类恶性肿瘤（包括膀胱癌）风险增加有关。然而，p-PD 对人尿路上皮细胞（SV-HUC-1）自噬的影响尚不清楚。在这项研究中，我们证明了 p-PD 可以激活 SV-HUC-1 细胞中的细胞外信号调节蛋白激酶 1/2（ERK1/2）信号通路。此外，我们通过电子显微镜观察到 p-PD 处理的 SV-HUC-1 细胞中自噬体增加。我们的结果显示，自噬体的重要调节因子浓度、Beclin-1 和微管相关蛋白轻链 3B（LC3B）呈递增趋势。相比之下，MEK 抑制剂（U0126）抑制了自噬，p-PD 对 ERK1/2、Beclin-1 和 LC3B 蛋白表达的影响（除了突变型 p53 外）。在这项研究中，我们证明了 p53 失活诱导强烈的自噬反应。最后，我们的结果表明，p-PD 可以激活 ERK1/2 信号通路和突变型 p53，导致 SV-HUC-1 细胞自噬的刺激。这些结果为我们理解 p-PD 诱导尿路上皮细胞死亡的机制提供了新的见解。
