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Bisphenol <scp>A</scp> induced apoptosis via oxidative stress generation involved <scp>Nrf2</scp> / <scp>HO</scp> ‐1 pathway and mitochondrial dependent pathways in human retinal pigment epithelium ( <scp>ARPE</scp> ‐19) cells
- Source :
- Environmental Toxicology. 37:131-141
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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.
- Subjects :
- endocrine system
biology
urogenital system
Chemistry
Health, Toxicology and Mutagenesis
Cytochrome c
AMPK
General Medicine
Management, Monitoring, Policy and Law
Mitochondrion
Toxicology
medicine.disease_cause
Cell biology
Heme oxygenase
Superoxide dismutase
Apoptosis
biology.protein
medicine
Apoptotic signaling pathway
hormones, hormone substitutes, and hormone antagonists
Oxidative stress
Subjects
Details
- ISSN :
- 15227278 and 15204081
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Environmental Toxicology
- Accession number :
- edsair.doi...........4496f31a6950a93d73540987cced595d