Bisphenol A induced apoptosis via oxidative stress generation involved Nrf2/HO‐1 pathway and mitochondrial dependent pathways in human retinal pigment epithelium (ARPE‐19) cells

• Published in: Environmental toxicology Vol. 37; no. 1; pp. 131 - 141
• Main Authors: Chiang, Yun‐Wei, Su, Chun‐Hung, Sun, Han‐Yin, Chen, Shih‐Pin, Chen, Chun‐Jung, Chen, Wen‐Ying, Chang, Chia‐Che, Chen, Chuan‐Mu, Kuan, Yu‐Hsiang
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.01.2022; Wiley Subscription Services, Inc
• Subjects: acetylcysteine; Antioxidants; Antioxidants - metabolism; Apoptosis; ARPE‐19 cells; BAX protein; Benzhydryl Compounds; Biological stress; Bisphenol A; blood; Caspase; caspase-3; caspase-9; Catalase; Cell Survival; Cells; Cytochrome; Cytochrome c; Cytochromes; Cytotoxicity; Degeneration; direct contact; ecotoxicology; Epithelium; Estrogens; Eye diseases; Heme; heme oxygenase (biliverdin-producing); Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hormones; Humans; Kinases; Macular degeneration; Membrane potential; Membranes; Mitochondria; Mitochondria - metabolism; mitochondrial dysfunction; mitochondrial membrane; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2/HO‐1 pathway; Oestrogens; Oxidative Stress; Oxygenase; Phenols; Phosphorylation; Proteins; Retina; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Sex hormones; Signal transduction; Superoxide dismutase; Toxicity; urine; ARPE-19 cells; apoptosis; bisphenol A; mitochondrial dysfunction; Nrf2/HO-1 pathway
• ISSN: 1520-4081; 1522-7278; 1522-7278
• DOI: 10.1002/tox.23384

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.