Bisphenol A (BPA) is an estrogen-like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE-19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE-19 cells. After BPA treatment, the expression of Bcl-XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase-9 to promote downstream caspase-3 leading to cytotoxicity. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) pathway play a major role in age-related macular degeneration. Our results showed that expression of HO-1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP-activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA-induced ROS generation and cytotoxicity were reduced by N-acetyl-l-cysteine. Taken together, these results suggest that BPA induced ARPE-19 cells via oxidative stress, which was associated with down regulated Nrf2/HO-1 pathway, and the mitochondria dependent apoptotic signaling pathway.

中文翻译：

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双酚 A 通过氧化应激诱导细胞凋亡，涉及人视网膜色素上皮 (ARPE-19) 细胞中的 Nrf2/HO-1 通路和线粒体依赖性通路

双酚 A (BPA) 是一种类雌激素化合物，也是一种环境激素，在日常生活中很常用。因此，它可能通过食物或直接接触进入人体，造成血液和尿液中的双酚A残留。因为大多数研究集中在生殖细胞或组织中的 BPA 分析，关于 BPA 对人视网膜色素上皮 (ARPE-19) 细胞的影响的证据尚不可用。因此，本研究探讨了 BPA 对 ARPE-19 细胞的细胞毒性。BPA处理后，线粒体中抗凋亡蛋白Bcl-XL的表达降低，而促凋亡蛋白Bax的表达增加。然后线粒体膜电位受到影响。BPA 线粒体膜电位的变化导致细胞色素 C 的释放，其激活 caspase-9 以促进下游 caspase-3 导致细胞毒性。核因子（红细胞衍生的 2）样 2（Nrf2）和血红素加氧酶 1（HO-1）通路在年龄相关性黄斑变性中起主要作用。我们的结果表明 HO-1 和 Nrf2 的表达被 BPA 抑制。Nrf2 下游抗氧化剂的超氧化物歧化酶和过氧化氢酶被 BPA 降解。AMP 激活激酶 (AMPK)，可调节 Nrf2 的磷酸化，BPA 降低 AMPK 表达的磷酸化。最后，N-乙酰基降低了 BPA 诱导的 ROS 生成和细胞毒性。Nrf2 下游抗氧化剂的超氧化物歧化酶和过氧化氢酶被 BPA 降解。AMP 激活激酶 (AMPK)，可调节 Nrf2 的磷酸化，BPA 降低 AMPK 表达的磷酸化。最后，N-乙酰基降低了 BPA 诱导的 ROS 生成和细胞毒性。Nrf2 下游抗氧化剂的超氧化物歧化酶和过氧化氢酶被 BPA 降解。AMP 激活激酶 (AMPK)，可调节 Nrf2 的磷酸化，BPA 降低 AMPK 表达的磷酸化。最后，N-乙酰基降低了 BPA 诱导的 ROS 生成和细胞毒性。l -半胱氨酸。总之，这些结果表明 BPA 通过氧化应激诱导 ARPE-19 细胞，这与下调 Nrf2/HO-1 通路和线粒体依赖性凋亡信号通路有关。