Abstract
The purpose of this study was to investigate the protective effects of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) in retinal pigment epithelial (RPE) cell damage. ARPE-19 cells, a human RPE cell line, were cultured with diHEP-DPA and Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), followed by exposure to BL. Cell viability and cell death rates were determined. Western blotting was performed to determine changes in apoptotic factors, mitogen-activated protein kinase (MAPK) family proteins, inflammatory proteins, and oxidative and carbonyl stresses. The levels of pro-inflammatory cytokines in the culture medium supernatants were also measured. Exposure to A2E and BL increased the ARPE-19 cell death rate, which was alleviated by diHEP-DPA in a concentration-dependent manner. A2E and BL treatments induced apoptosis in ARPE-19 cells, which was also alleviated by diHEP-DPA. Analysis of the relationship with MAPK proteins revealed that the expression of p-JNK and p-P38 increased after A2E and BL treatments and decreased with exposure to diHEP-DPA in a concentration-dependent manner. DiHEP-DPA also affected the inflammatory response by suppressing the expression of inflammatory proteins and the production of pro-inflammatory cytokines. Furthermore, it was shown that diHEP-DPA regulated the proteins related to oxidative and carbonyl stresses. Taken together, our results provide evidence that diHEP-DPA can inhibit cell damage caused by A2E and BL exposure at the cellular level by controlling various pathways involved in apoptosis and inflammatory responses.